371 results on '"Translational Neuroscience"'
Search Results
2. SEMA6A drives GnRH neuron-dependent puberty onset by tuning median eminence vascular permeability
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TN groep Pasterkamp, Brain, Translational Neuroscience, Regenerative Medicine and Stem Cells, Lettieri, Antonella, Oleari, Roberto, van den Munkhof, Marleen Hester, van Battum, Eljo Yvette, Verhagen, Marieke Geerte, Tacconi, Carlotta, Spreafico, Marco, Paganoni, Alyssa Julia Jennifer, Azzarelli, Roberta, Andre’, Valentina, Amoruso, Federica, Palazzolo, Luca, Eberini, Ivano, Dunkel, Leo, Howard, Sasha Rose, Fantin, Alessandro, Pasterkamp, Ronald Jeroen, Cariboni, Anna, TN groep Pasterkamp, Brain, Translational Neuroscience, Regenerative Medicine and Stem Cells, Lettieri, Antonella, Oleari, Roberto, van den Munkhof, Marleen Hester, van Battum, Eljo Yvette, Verhagen, Marieke Geerte, Tacconi, Carlotta, Spreafico, Marco, Paganoni, Alyssa Julia Jennifer, Azzarelli, Roberta, Andre’, Valentina, Amoruso, Federica, Palazzolo, Luca, Eberini, Ivano, Dunkel, Leo, Howard, Sasha Rose, Fantin, Alessandro, Pasterkamp, Ronald Jeroen, and Cariboni, Anna
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- 2023
3. Purkinje cell microzones mediate distinct kinematics of a single movement
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TN groep Pasterkamp, Brain, Translational Neuroscience, Regenerative Medicine and Stem Cells, Blot, François G.C., White, Joshua J., van Hattem, Amy, Scotti, Licia, Balaji, Vaishnavi, Adolfs, Youri, Pasterkamp, R. Jeroen, De Zeeuw, Chris I., Schonewille, Martijn, TN groep Pasterkamp, Brain, Translational Neuroscience, Regenerative Medicine and Stem Cells, Blot, François G.C., White, Joshua J., van Hattem, Amy, Scotti, Licia, Balaji, Vaishnavi, Adolfs, Youri, Pasterkamp, R. Jeroen, De Zeeuw, Chris I., and Schonewille, Martijn
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- 2023
4. Development, wiring and function of dopamine neuron subtypes
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TN groep Pasterkamp, Brain, Translational Neuroscience, Regenerative Medicine and Stem Cells, Garritsen, Oxana, van Battum, Eljo Y., Grossouw, Laurens M., Pasterkamp, R. Jeroen, TN groep Pasterkamp, Brain, Translational Neuroscience, Regenerative Medicine and Stem Cells, Garritsen, Oxana, van Battum, Eljo Y., Grossouw, Laurens M., and Pasterkamp, R. Jeroen
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- 2023
5. In vivo imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status – A pilot study combining PET and deuterium metabolic imaging
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In Vivo NMR ISI, Circulatory Health, Brain, Translational Neuroscience, Cancer, Stroke, Meerwaldt, Anu E., Straathof, Milou, Oosterveld, Wija, van Heijningen, Caroline L., van Leent, Mandy M.T., Toner, Yohana C., Munitz, Jazz, Teunissen, Abraham J.P., Daemen, Charlotte C., van der Toorn, Annette, van Vliet, Gerard, van Tilborg, Geralda A.F., De Feyter, Henk M., de Graaf, Robin A., Hol, Elly M., Mulder, Willem J.M., Dijkhuizen, Rick M., In Vivo NMR ISI, Circulatory Health, Brain, Translational Neuroscience, Cancer, Stroke, Meerwaldt, Anu E., Straathof, Milou, Oosterveld, Wija, van Heijningen, Caroline L., van Leent, Mandy M.T., Toner, Yohana C., Munitz, Jazz, Teunissen, Abraham J.P., Daemen, Charlotte C., van der Toorn, Annette, van Vliet, Gerard, van Tilborg, Geralda A.F., De Feyter, Henk M., de Graaf, Robin A., Hol, Elly M., Mulder, Willem J.M., and Dijkhuizen, Rick M.
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- 2023
6. Molecular profile and response to energy deficit of leptin-receptor neurons in the lateral hypothalamus
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TN groep Adan, Brain, Cancer, Translational Neuroscience, Kakava-Georgiadou, N, Drkelic, V, Garner, K M, Luijendijk, M C M, Basak, O, Adan, R A H, TN groep Adan, Brain, Cancer, Translational Neuroscience, Kakava-Georgiadou, N, Drkelic, V, Garner, K M, Luijendijk, M C M, Basak, O, and Adan, R A H
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- 2022
7. Differential compartmentalization of myeloid cell phenotypes and responses towards the CNS in Alzheimer's disease
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TN groep Hol, Brain, Translational Neuroscience, Cancer, Fernández Zapata, Camila, Giacomello, Ginevra, Spruth, Eike J, Middeldorp, Jinte, Gallaccio, Gerardina, Dehlinger, Adeline, Dames, Claudia, Leman, Julia K H, van Dijk, Roland E, Meisel, Andreas, Schlickeiser, Stephan, Kunkel, Desiree, Hol, Elly M, Paul, Friedemann, Parr, Maria Kristina, Priller, Josef, Böttcher, Chotima, TN groep Hol, Brain, Translational Neuroscience, Cancer, Fernández Zapata, Camila, Giacomello, Ginevra, Spruth, Eike J, Middeldorp, Jinte, Gallaccio, Gerardina, Dehlinger, Adeline, Dames, Claudia, Leman, Julia K H, van Dijk, Roland E, Meisel, Andreas, Schlickeiser, Stephan, Kunkel, Desiree, Hol, Elly M, Paul, Friedemann, Parr, Maria Kristina, Priller, Josef, and Böttcher, Chotima
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- 2022
8. Best practice standards for circular RNA research
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Translational Neuroscience, Brain, Regenerative Medicine and Stem Cells, Nielsen, Anne F., Bindereif, Albrecht, Bozzoni, Irene, Hanan, Mor, Hansen, Thomas B., Irimia, Manuel, Kadener, Sebastian, Kristensen, Lasse S., Legnini, Ivano, Morlando, Mariangela, Jarlstad Olesen, Morten T., Pasterkamp, R. Jeroen, Preibisch, Stephan, Rajewsky, Nikolaus, Suenkel, Christin, Kjems, Jørgen, Translational Neuroscience, Brain, Regenerative Medicine and Stem Cells, Nielsen, Anne F., Bindereif, Albrecht, Bozzoni, Irene, Hanan, Mor, Hansen, Thomas B., Irimia, Manuel, Kadener, Sebastian, Kristensen, Lasse S., Legnini, Ivano, Morlando, Mariangela, Jarlstad Olesen, Morten T., Pasterkamp, R. Jeroen, Preibisch, Stephan, Rajewsky, Nikolaus, Suenkel, Christin, and Kjems, Jørgen
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- 2022
9. Astrogenesis in the murine dentate gyrus is a life‐long and dynamic process
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Translational Neuroscience, Cancer, Brain, Basak, Onur, Translational Neuroscience, Cancer, Brain, and Basak, Onur
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- 2022
10. Microglial transcriptomics meets genetics: new disease leads (Feb, 10.1038/s41582-022-00633-w, 2022): Microglial transcriptomics meets genetics: new disease leads (Nature Reviews Neurology, (2022), 18, 4, (191-192), 10.1038/s41582-022-00633-w)
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Translational Neuroscience, Brain, Cancer, Regenerative Medicine and Stem Cells, Hol, Elly M., Pasterkamp, R. Jeroen, Translational Neuroscience, Brain, Cancer, Regenerative Medicine and Stem Cells, Hol, Elly M., and Pasterkamp, R. Jeroen
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- 2022
11. Single-cell profiling of human subventricular zone progenitors identifies SFRP1 as a target to re-activate progenitors
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TN groep Hol, TN groep Pasterkamp, Translational Neuroscience, Cancer, Brain, Regenerative Medicine and Stem Cells, Donega, Vanessa, van der Geest, Astrid T., Sluijs, Jacqueline A., van Dijk, Roland E., Wang, Chi Chiu, Basak, Onur, Pasterkamp, R. Jeroen, Hol, Elly M., TN groep Hol, TN groep Pasterkamp, Translational Neuroscience, Cancer, Brain, Regenerative Medicine and Stem Cells, Donega, Vanessa, van der Geest, Astrid T., Sluijs, Jacqueline A., van Dijk, Roland E., Wang, Chi Chiu, Basak, Onur, Pasterkamp, R. Jeroen, and Hol, Elly M.
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- 2022
12. Microglial transcriptomics meets genetics: new disease leads
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Translational Neuroscience, Brain, Cancer, Regenerative Medicine and Stem Cells, Hol, Elly M, Pasterkamp, R Jeroen, Translational Neuroscience, Brain, Cancer, Regenerative Medicine and Stem Cells, Hol, Elly M, and Pasterkamp, R Jeroen
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- 2022
13. Author Correction: Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology (Nature Genetics, (2021), 53, 12, (1636-1648), 10.1038/s41588-021-00973-1)
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Neurologen, AIOS Psychiatrie, Neurogenetica, Genetica Klinische Genetica, Opleiding Neurologie, Brain, Hersenen-Bedrijfsvoering, Translational Neuroscience, Regenerative Medicine and Stem Cells, Projectafdeling ALS, Genetic Risks, Neuromuscular Disorders, SLALOM Consortium, Neurologen, AIOS Psychiatrie, Neurogenetica, Genetica Klinische Genetica, Opleiding Neurologie, Brain, Hersenen-Bedrijfsvoering, Translational Neuroscience, Regenerative Medicine and Stem Cells, Projectafdeling ALS, Genetic Risks, Neuromuscular Disorders, and SLALOM Consortium
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- 2022
14. Analysis of the circRNA and T-UCR populations identifies convergent pathways in mouse and human models of Rett syndrome
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TN groep Pasterkamp, Translational Neuroscience, Brain, Regenerative Medicine and Stem Cells, Siqueira, Edilene, Obiols-Guardia, Aida, Jorge-Torres, Olga C., Oliveira-Mateos, Cristina, Soler, Marta, Ramesh-Kumar, Deepthi, Setién, Fernando, van Rossum, Daniëlle, Pascual-Alonso, Ainhoa, Xiol, Clara, Ivan, Cristina, Shimizu, Masayoshi, Armstrong, Judith, Calin, George A., Pasterkamp, R. Jeroen, Esteller, Manel, Guil, Sonia, TN groep Pasterkamp, Translational Neuroscience, Brain, Regenerative Medicine and Stem Cells, Siqueira, Edilene, Obiols-Guardia, Aida, Jorge-Torres, Olga C., Oliveira-Mateos, Cristina, Soler, Marta, Ramesh-Kumar, Deepthi, Setién, Fernando, van Rossum, Daniëlle, Pascual-Alonso, Ainhoa, Xiol, Clara, Ivan, Cristina, Shimizu, Masayoshi, Armstrong, Judith, Calin, George A., Pasterkamp, R. Jeroen, Esteller, Manel, and Guil, Sonia
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- 2022
15. GFAP splice variants fine-tune glioma cell invasion and tumour dynamics by modulating migration persistence
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TN groep Hol, Brain, Neurochirurgie, Cancer, Hubrecht Institute with UMC, Translational Neuroscience, Uceda-Castro, Rebeca, van Asperen, Jessy V., Vennin, Claire, Sluijs, Jacqueline A., van Bodegraven, Emma J., Margarido, Andreia S., Robe, Pierre A.J., van Rheenen, Jacco, Hol, Elly M., TN groep Hol, Brain, Neurochirurgie, Cancer, Hubrecht Institute with UMC, Translational Neuroscience, Uceda-Castro, Rebeca, van Asperen, Jessy V., Vennin, Claire, Sluijs, Jacqueline A., van Bodegraven, Emma J., Margarido, Andreia S., Robe, Pierre A.J., van Rheenen, Jacco, and Hol, Elly M.
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- 2022
16. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
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Neurologen, AIOS Psychiatrie, Neurogenetica, Genetica Klinische Genetica, Opleiding Neurologie, Brain, Hersenen-Bedrijfsvoering, Translational Neuroscience, Regenerative Medicine and Stem Cells, Projectafdeling ALS, SLALOM Consortium, Neurologen, AIOS Psychiatrie, Neurogenetica, Genetica Klinische Genetica, Opleiding Neurologie, Brain, Hersenen-Bedrijfsvoering, Translational Neuroscience, Regenerative Medicine and Stem Cells, Projectafdeling ALS, and SLALOM Consortium
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- 2021
17. Publisher Correction: LifeTime and improving European healthcare through cell-based interceptive medicine
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Public Health Practice, Medical Humanities Onderzoek Team 2, Child Health, Regenerative Medicine and Stem Cells, JC onderzoeksprogramma Methodologie, CMM Sectie Molecular Cancer Research, Cancer, Hubrecht Institute with UMC, Onderzoek, Brain, Translational Neuroscience, LifeTime Community Working Groups, Public Health Practice, Medical Humanities Onderzoek Team 2, Child Health, Regenerative Medicine and Stem Cells, JC onderzoeksprogramma Methodologie, CMM Sectie Molecular Cancer Research, Cancer, Hubrecht Institute with UMC, Onderzoek, Brain, Translational Neuroscience, and LifeTime Community Working Groups
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- 2021
18. A directional 3D neurite outgrowth model for studying motor axon biology and disease
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Translational Neuroscience, Brain, Regenerative Medicine and Stem Cells, Spijkers, Xandor M., Pasteuning-Vuhman, Svetlana, Dorleijn, Jennifa C., Vulto, Paul, Wevers, Nienke R., Pasterkamp, R. Jeroen, Translational Neuroscience, Brain, Regenerative Medicine and Stem Cells, Spijkers, Xandor M., Pasteuning-Vuhman, Svetlana, Dorleijn, Jennifa C., Vulto, Paul, Wevers, Nienke R., and Pasterkamp, R. Jeroen
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- 2021
19. Reactive astrocyte nomenclature, definitions, and future directions
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Translational Neuroscience, Brain, Cancer, Escartin, Carole, Galea, Elena, Lakatos, András, O’Callaghan, James P., Petzold, Gabor C., Serrano-Pozo, Alberto, Steinhäuser, Christian, Volterra, Andrea, Carmignoto, Giorgio, Agarwal, Amit, Allen, Nicola J., Araque, Alfonso, Barbeito, Luis, Barzilai, Ari, Bergles, Dwight E., Bonvento, Gilles, Butt, Arthur M., Chen, Wei Ting, Cohen-Salmon, Martine, Cunningham, Colm, Deneen, Benjamin, De Strooper, Bart, Díaz-Castro, Blanca, Farina, Cinthia, Freeman, Marc, Gallo, Vittorio, Goldman, James E., Goldman, Steven A., Götz, Magdalena, Gutiérrez, Antonia, Haydon, Philip G., Heiland, Dieter H., Hol, Elly M., Holt, Matthew G., Iino, Masamitsu, Kastanenka, Ksenia V., Kettenmann, Helmut, Khakh, Baljit S., Koizumi, Schuichi, Lee, C. Justin, Liddelow, Shane A., MacVicar, Brian A., Magistretti, Pierre, Messing, Albee, Mishra, Anusha, Molofsky, Anna V., Murai, Keith K., Norris, Christopher M., Okada, Seiji, Oliet, Stéphane H.R., Oliveira, João F., Panatier, Aude, Parpura, Vladimir, Pekna, Marcela, Pekny, Milos, Pellerin, Luc, Perea, Gertrudis, Pérez-Nievas, Beatriz G., Pfrieger, Frank W., Poskanzer, Kira E., Quintana, Francisco J., Ransohoff, Richard M., Riquelme-Perez, Miriam, Robel, Stefanie, Rose, Christine R., Rothstein, Jeffrey D., Rouach, Nathalie, Rowitch, David H., Semyanov, Alexey, Sirko, Swetlana, Sontheimer, Harald, Swanson, Raymond A., Vitorica, Javier, Wanner, Ina Beate, Wood, Levi B., Wu, Jiaqian, Zheng, Binhai, Zimmer, Eduardo R., Zorec, Robert, Sofroniew, Michael V., Verkhratsky, Alexei, Translational Neuroscience, Brain, Cancer, Escartin, Carole, Galea, Elena, Lakatos, András, O’Callaghan, James P., Petzold, Gabor C., Serrano-Pozo, Alberto, Steinhäuser, Christian, Volterra, Andrea, Carmignoto, Giorgio, Agarwal, Amit, Allen, Nicola J., Araque, Alfonso, Barbeito, Luis, Barzilai, Ari, Bergles, Dwight E., Bonvento, Gilles, Butt, Arthur M., Chen, Wei Ting, Cohen-Salmon, Martine, Cunningham, Colm, Deneen, Benjamin, De Strooper, Bart, Díaz-Castro, Blanca, Farina, Cinthia, Freeman, Marc, Gallo, Vittorio, Goldman, James E., Goldman, Steven A., Götz, Magdalena, Gutiérrez, Antonia, Haydon, Philip G., Heiland, Dieter H., Hol, Elly M., Holt, Matthew G., Iino, Masamitsu, Kastanenka, Ksenia V., Kettenmann, Helmut, Khakh, Baljit S., Koizumi, Schuichi, Lee, C. Justin, Liddelow, Shane A., MacVicar, Brian A., Magistretti, Pierre, Messing, Albee, Mishra, Anusha, Molofsky, Anna V., Murai, Keith K., Norris, Christopher M., Okada, Seiji, Oliet, Stéphane H.R., Oliveira, João F., Panatier, Aude, Parpura, Vladimir, Pekna, Marcela, Pekny, Milos, Pellerin, Luc, Perea, Gertrudis, Pérez-Nievas, Beatriz G., Pfrieger, Frank W., Poskanzer, Kira E., Quintana, Francisco J., Ransohoff, Richard M., Riquelme-Perez, Miriam, Robel, Stefanie, Rose, Christine R., Rothstein, Jeffrey D., Rouach, Nathalie, Rowitch, David H., Semyanov, Alexey, Sirko, Swetlana, Sontheimer, Harald, Swanson, Raymond A., Vitorica, Javier, Wanner, Ina Beate, Wood, Levi B., Wu, Jiaqian, Zheng, Binhai, Zimmer, Eduardo R., Zorec, Robert, Sofroniew, Michael V., and Verkhratsky, Alexei
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- 2021
20. Systemic delivery of antagomirs during blood-brain barrier disruption is disease-modifying in experimental epilepsy
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TN groep Pasterkamp, Brain, Translational Neuroscience, Regenerative Medicine and Stem Cells, Reschke, Cristina R., Silva, Luiz F.A., Vangoor, Vamshidhar R., Rosso, Massimo, David, Bastian, Cavanagh, Brenton L., Connolly, Niamh M.C., Brennan, Gary P., Sanz-Rodriguez, Amaya, Mooney, Catherine, Batool, Aasia, Greene, Chris, Brennan, Marian, Conroy, Ronan M., Rüber, Theodor, Prehn, Jochen H.M., Campbell, Matthew, Pasterkamp, R. Jeroen, Henshall, David C., TN groep Pasterkamp, Brain, Translational Neuroscience, Regenerative Medicine and Stem Cells, Reschke, Cristina R., Silva, Luiz F.A., Vangoor, Vamshidhar R., Rosso, Massimo, David, Bastian, Cavanagh, Brenton L., Connolly, Niamh M.C., Brennan, Gary P., Sanz-Rodriguez, Amaya, Mooney, Catherine, Batool, Aasia, Greene, Chris, Brennan, Marian, Conroy, Ronan M., Rüber, Theodor, Prehn, Jochen H.M., Campbell, Matthew, Pasterkamp, R. Jeroen, and Henshall, David C.
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- 2021
21. Distinct non-inflammatory signature of microglia in post-mortem brain tissue of patients with major depressive disorder
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AIOS Psychiatrie, TN groep Pasterkamp, Onderzoeksgroep 2, Brain, Psychiatrie_Medisch, Translational Neuroscience, Cancer, TN groep Hol, Onderzoeksgroep 11, MMB Research line 3b, Psychiatric Donor Program of the Netherlands Brain Bank (NBB-Psy), AIOS Psychiatrie, TN groep Pasterkamp, Onderzoeksgroep 2, Brain, Psychiatrie_Medisch, Translational Neuroscience, Cancer, TN groep Hol, Onderzoeksgroep 11, MMB Research line 3b, and Psychiatric Donor Program of the Netherlands Brain Bank (NBB-Psy)
- Published
- 2021
22. Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
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TN groep Adan, Brain, Translational Neuroscience, Neurogenetica, Circulatory Health, Onderzoek, Arts-assistenten Kinderen, Eating Disorders Working Group of the Psychiatric Genomics Consortium, International Headache Genetics Consortium, 23andMe Research Team, TN groep Adan, Brain, Translational Neuroscience, Neurogenetica, Circulatory Health, Onderzoek, Arts-assistenten Kinderen, Eating Disorders Working Group of the Psychiatric Genomics Consortium, International Headache Genetics Consortium, and 23andMe Research Team
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- 2020
23. Nolz1 expression is required in dopaminergic axon guidance and striatal innervation
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TN groep Pasterkamp, Brain, Translational Neuroscience, Regenerative Medicine and Stem Cells, Soleilhavoup, Clement, Travaglio, Marco, Patrick, Kieran, Garção, Pedro, Boobalan, Elangovan, Adolfs, Youri, Spriggs, Ruth V., Moles-Garcia, Emma, Dhiraj, Dalbir, Oosterveen, Tony, Ferri, Sarah L., Abel, Ted, Brodkin, Edward S., Pasterkamp, R. Jeroen, Brooks, Brian P., Panman, Lia, TN groep Pasterkamp, Brain, Translational Neuroscience, Regenerative Medicine and Stem Cells, Soleilhavoup, Clement, Travaglio, Marco, Patrick, Kieran, Garção, Pedro, Boobalan, Elangovan, Adolfs, Youri, Spriggs, Ruth V., Moles-Garcia, Emma, Dhiraj, Dalbir, Oosterveen, Tony, Ferri, Sarah L., Abel, Ted, Brodkin, Edward S., Pasterkamp, R. Jeroen, Brooks, Brian P., and Panman, Lia
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- 2020
24. The reduction of astrocytes and brain volume loss in anorexia nervosa—the impact of starvation and refeeding in a rodent model
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Translational Neuroscience, Frintrop, Linda, Trinh, Stefanie, Liesbrock, Johanna, Leunissen, Christina, Kempermann, Julia, Etdöger, Serhat, Kas, Martien J., Tolba, René, Heussen, Nicole, Neulen, Joseph, Konrad, Kerstin, Päfgen, Vera, Kiessling, Fabian, Herpertz-Dahlmann, Beate, Beyer, Cordian, Seitz, Jochen, Translational Neuroscience, Frintrop, Linda, Trinh, Stefanie, Liesbrock, Johanna, Leunissen, Christina, Kempermann, Julia, Etdöger, Serhat, Kas, Martien J., Tolba, René, Heussen, Nicole, Neulen, Joseph, Konrad, Kerstin, Päfgen, Vera, Kiessling, Fabian, Herpertz-Dahlmann, Beate, Beyer, Cordian, and Seitz, Jochen
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- 2019
25. Reproducibility via coordinated standardization: a multi-center study in a S hank2 genetic rat model for Autism Spectrum Disorders
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Translational Neuroscience, Arroyo-Araujo, María, Graf, Radka, Maco, Martine, van Dam, Elsbeth, Schenker, Esther, Drinkenburg, Wilhelmus, Koopmans, Bastijn, de Boer, Sietse F., Cullum-Doyle, Michaela, Noldus, Lucas P.J.J., Loos, Maarten, van Dommelen, Wil, Spooren, Will, Biemans, Barbara, Buhl, Derek L., Kas, Martien J., Translational Neuroscience, Arroyo-Araujo, María, Graf, Radka, Maco, Martine, van Dam, Elsbeth, Schenker, Esther, Drinkenburg, Wilhelmus, Koopmans, Bastijn, de Boer, Sietse F., Cullum-Doyle, Michaela, Noldus, Lucas P.J.J., Loos, Maarten, van Dommelen, Wil, Spooren, Will, Biemans, Barbara, Buhl, Derek L., and Kas, Martien J.
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- 2019
26. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa
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TN groep Adan, Brain, Circulatory Health, Translational Neuroscience, Hersenen-Bedrijfsvoering, Neurogenetica, Watson, Hunna J, Yilmaz, Zeynep, Thornton, Laura M, Hübel, Christopher, Coleman, Jonathan R I, Gaspar, Héléna A, Bryois, Julien, Hinney, Anke, Leppä, Virpi M, Mattheisen, Manuel, Medland, Sarah E, Ripke, Stephan, Yao, Shuyang, Giusti-Rodríguez, Paola, Hanscombe, Ken B, Purves, Kirstin L, Adan, Roger A H, Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole A, Baker, Jessica H, Berrettini, Wade H, Boehm, Ilka, Boni, Claudette, Perica, Vesna Boraska, Buehren, Katharina, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Cone, Roger D, Courtet, Philippe, Crow, Scott, Crowley, James J, Danner, Unna N, Davis, Oliver S P, de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E, Dick, Danielle M, Dikeos, Dimitris, Dina, Christian, Dmitrzak-Weglarz, Monika, Docampo, Elisa, Duncan, Laramie E, Egberts, Karin, Kas, Martien J H, Lin, Bochao Danae, Ophoff, Roel A, Luykx, Jurjen, Anorexia Nervosa Genetics Initiative, TN groep Adan, Brain, Circulatory Health, Translational Neuroscience, Hersenen-Bedrijfsvoering, Neurogenetica, Watson, Hunna J, Yilmaz, Zeynep, Thornton, Laura M, Hübel, Christopher, Coleman, Jonathan R I, Gaspar, Héléna A, Bryois, Julien, Hinney, Anke, Leppä, Virpi M, Mattheisen, Manuel, Medland, Sarah E, Ripke, Stephan, Yao, Shuyang, Giusti-Rodríguez, Paola, Hanscombe, Ken B, Purves, Kirstin L, Adan, Roger A H, Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole A, Baker, Jessica H, Berrettini, Wade H, Boehm, Ilka, Boni, Claudette, Perica, Vesna Boraska, Buehren, Katharina, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Cone, Roger D, Courtet, Philippe, Crow, Scott, Crowley, James J, Danner, Unna N, Davis, Oliver S P, de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E, Dick, Danielle M, Dikeos, Dimitris, Dina, Christian, Dmitrzak-Weglarz, Monika, Docampo, Elisa, Duncan, Laramie E, Egberts, Karin, Kas, Martien J H, Lin, Bochao Danae, Ophoff, Roel A, Luykx, Jurjen, and Anorexia Nervosa Genetics Initiative
- Published
- 2019
27. Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa
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TN groep Adan, Brain, Circulatory Health, Translational Neuroscience, TN Onderwijs, Huckins, Laura M., Hatzikotoulas, Konstantinos, Southam, L., Thornton, Laura M., Steinberg, J.S., Aguilera-McKay, F, Treasure, J., Schmidt, U., Gunasinghe, C, Romero, Atocha, Curtis, Charles, Rhodes, Davina H., Bernelot Moens, Hein J, Kalsi, Gursharan, Dempster, D, Leung, R, Keohane, A, Burghardt, Roland, Ehrlich, S., Hebebrand, J., Hinney, A., Ludolph, A., Walton, Esther, Deloukas, P., Hofman, A., Palotie, A., Palta, P., Van Rooij, Frank J A, Stirrups, Kathleen, Adan, R, Boni, Claudette, Cone, Roger, Dedoussis, George, Furth, E.E., Gonidakis, Fragiskos, Gorwood, P., Hudson, Thomas J., Kaprio, Jaakko, Kas, M, Keski-Rahonen, A, Kiezebrink, K., Knudsen, Gun Peggy S., Slof-Op 't Landt, M C T, Maj, Mario, Monteleone, Alessio Maria, Monteleone, Palmiero, Raevuori, A H, Reichborn-Kjennerud, Ted, Tozzi, F., Tsitsika, Artemis, Eating Disorder Working Group of the Psychiatric Genomics Consortium, TN groep Adan, Brain, Circulatory Health, Translational Neuroscience, TN Onderwijs, Huckins, Laura M., Hatzikotoulas, Konstantinos, Southam, L., Thornton, Laura M., Steinberg, J.S., Aguilera-McKay, F, Treasure, J., Schmidt, U., Gunasinghe, C, Romero, Atocha, Curtis, Charles, Rhodes, Davina H., Bernelot Moens, Hein J, Kalsi, Gursharan, Dempster, D, Leung, R, Keohane, A, Burghardt, Roland, Ehrlich, S., Hebebrand, J., Hinney, A., Ludolph, A., Walton, Esther, Deloukas, P., Hofman, A., Palotie, A., Palta, P., Van Rooij, Frank J A, Stirrups, Kathleen, Adan, R, Boni, Claudette, Cone, Roger, Dedoussis, George, Furth, E.E., Gonidakis, Fragiskos, Gorwood, P., Hudson, Thomas J., Kaprio, Jaakko, Kas, M, Keski-Rahonen, A, Kiezebrink, K., Knudsen, Gun Peggy S., Slof-Op 't Landt, M C T, Maj, Mario, Monteleone, Alessio Maria, Monteleone, Palmiero, Raevuori, A H, Reichborn-Kjennerud, Ted, Tozzi, F., Tsitsika, Artemis, and Eating Disorder Working Group of the Psychiatric Genomics Consortium
- Published
- 2018
28. A genome-wide association study of anorexia nervosa suggests a risk locus implicated in dysregulated leptin signaling
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TN groep Adan, Brain, Circulatory Health, Translational Neuroscience, Genetica Groep Koeleman, Child Health, Onderzoek, Pathologie, AIOS Psychiatrie, Li, Dong, Chang, Xiao, Connolly, John J., Tian, Lifeng, Liu, Yichuan, Bhoj, Elizabeth J., Robinson, Nora, Abrams, Debra, Li, Yun R., Bradfield, Jonathan P., Kim, Cecilia E., Li, Jin, Wang, Fengxiang, Snyder, James, Lemma, Maria, Hou, Cuiping, Wei, Zhi, Guo, Yiran, Qiu, Haijun, Mentch, Frank D., Thomas, Kelly A., Chiavacci, Rosetta M., Cone, Roger, Li, Bingshan, Sleiman, Patrick A., Hakonarson, Hakon, Perica, Vesna Boraska, Franklin, Christopher S., Floyd, James A.B., Thornton, Laura M., Huckins, Laura M., Southam, Lorraine, Rayner, William N, Tachmazidou, Ioanna, Schmidt, Ulrike, Tozzi, Federica, Kiezebrink, Kirsty, Hebebrand, Johannes, Gorwood, Philip, Adan, Roger A.H., Kas, Martien J.H., Favaro, Angela, Santonastaso, Paolo, Fernánde-Aranda, Fernando, Gratacos, Monica, Rybakowski, Filip, Dmitrzak-Weglarz, Monika, Kaprio, Jaakko, Keski-Rahkonen, Anna, Raevuori-Helkamaa, Anu, Furth, Eric F.Van, Slof-Opt Landt, Margarita C.T., Hudson, James I., Reichborn-Kjennerud, Ted, Knudsen, Gun Peggy S., Monteleone, Palmiero, Karwautz, Andreas, Berrettini, Wade H., Schork, Nicholas J., Ando, Tetsuya, Inoko, Hidetoshi, Esko, Toñu, Fischer, Krista, Männik, Katrin, Metspalu, Andres, Baker, Jessica H., DeSocio, Janiece E., Hilliard, Christopher E., O'Toole, Julie K., Pantel, Jacques, Szatkiewicz, Jin P., Zerwas, Stephanie, Davis, Oliver S P, Helder, Sietske, Bühren, Katharina, Burghardt, Roland, De Zwaan, Martina, Egberts, Karin, Ehrlich, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Imgart, Hartmut, Scherag, André, Zipfel, Stephan, Boni, Claudette, Ramoz, Nicolas, Versini, Audrey, Danner, Unna N., Hendriks, Judith, Koeleman, Bobby P.C., Ophoff, Roel A., Strengman, Eric, van Elburg, Annemarie A., Bruson, Alice, Clementi, Maurizio, Degortes, Daniela, Forzan, Monica, Tenconi, Elena, Docampo, Elisa, Escaramís, Geòrgia, Jiménez-Murcia, Susana, Lissowska, Jolanta, Rajewski, Andrzej, Szeszenia-Dabrowska, Neonila, Slopien, Agnieszka, Hauser, Joanna, Karhunen, Leila, Meulenbelt, Ingrid, Slagboom, P. Eline, Tortorella, Alfonso, Maj, Mario, Dedoussis, George, DIkeos, DImitris, Gonidakis, Fragiskos, Tziouvas, Konstantinos, Tsitsika, Artemis, Papezova, Hana, Slachtova, Lenka, Martaskova, Debora, Kennedy, James L., Levitan, Robert D., Yilmaz, Zeynep, Huemer, Julia, Koubek, Doris, Merl, Elisabeth, Wagner, Gudrun, Lichtenstein, Paul, Breen, Gerome, Cohen-Woods, Sarah, Farmer, Anne, McGuffin, Peter, Cichon, Sven, Giegling, Ina, Herms, Stefan, Rujescu, Dan, Schreiber, Stefan, Wichmann, H-Erich, Dina, Christian, Sladek, Rob, Gambaro, Giovanni, Soranzo, Nicole, Julia, Antonio, Marsal, Sara, Rabionet, Raquel, Gaborieau, Valerie, DIck, Danielle M., Palotie, Aarno, Ripatti, Samuli, Widén, Elisabeth, Andreassen, Ole A., Espeseth, Thomas, Lundervold, Astri J, Reinvang, Ivar, Steen, Vidar M., Le Hellard, Stephanie, Mattingsdal, Morten, Ntalla, Ioanna, Bencko, Vladimir, Foretova, Lenka, Janout, Vladimir, Navratilova, Marie, Gallinger, Steven, Pinto, Dalila, Scherer, Stephen W., Aschauer, Harald, Carlberg, Laura, Schosser, Alexandra, Alfredsson, Lars, Ding, Bo, Klareskog, Lars, Padyukov, Leonid, Finan, Chris, Kalsi, Gursharan, Roberts, Marion, Barrett, Jeff C., Estivill, Xavier, Hinney, Anke, Sullivan, Patrick F, Zeggini, Eleftheria, Bulik, Cynthia M., Brandt, Harry, Crawford, Steve, Crow, Scott, Fichter, Manfred M., Halmi, Katherine A., Johnson, Craig, Kaplan, Allan S., La Via, Maria C., Mitchell, James R., Strober, Michael, Rotondo, Alessandro, Treasure, Janet, Woodside, D. Blake, Keel, Pamela K., Klump, Kelly L., Lilenfeld, Lisa, Bergen, Andrew W., Kaye, Walter, Magistretti, Pierre, TN groep Adan, Brain, Circulatory Health, Translational Neuroscience, Genetica Groep Koeleman, Child Health, Onderzoek, Pathologie, AIOS Psychiatrie, Li, Dong, Chang, Xiao, Connolly, John J., Tian, Lifeng, Liu, Yichuan, Bhoj, Elizabeth J., Robinson, Nora, Abrams, Debra, Li, Yun R., Bradfield, Jonathan P., Kim, Cecilia E., Li, Jin, Wang, Fengxiang, Snyder, James, Lemma, Maria, Hou, Cuiping, Wei, Zhi, Guo, Yiran, Qiu, Haijun, Mentch, Frank D., Thomas, Kelly A., Chiavacci, Rosetta M., Cone, Roger, Li, Bingshan, Sleiman, Patrick A., Hakonarson, Hakon, Perica, Vesna Boraska, Franklin, Christopher S., Floyd, James A.B., Thornton, Laura M., Huckins, Laura M., Southam, Lorraine, Rayner, William N, Tachmazidou, Ioanna, Schmidt, Ulrike, Tozzi, Federica, Kiezebrink, Kirsty, Hebebrand, Johannes, Gorwood, Philip, Adan, Roger A.H., Kas, Martien J.H., Favaro, Angela, Santonastaso, Paolo, Fernánde-Aranda, Fernando, Gratacos, Monica, Rybakowski, Filip, Dmitrzak-Weglarz, Monika, Kaprio, Jaakko, Keski-Rahkonen, Anna, Raevuori-Helkamaa, Anu, Furth, Eric F.Van, Slof-Opt Landt, Margarita C.T., Hudson, James I., Reichborn-Kjennerud, Ted, Knudsen, Gun Peggy S., Monteleone, Palmiero, Karwautz, Andreas, Berrettini, Wade H., Schork, Nicholas J., Ando, Tetsuya, Inoko, Hidetoshi, Esko, Toñu, Fischer, Krista, Männik, Katrin, Metspalu, Andres, Baker, Jessica H., DeSocio, Janiece E., Hilliard, Christopher E., O'Toole, Julie K., Pantel, Jacques, Szatkiewicz, Jin P., Zerwas, Stephanie, Davis, Oliver S P, Helder, Sietske, Bühren, Katharina, Burghardt, Roland, De Zwaan, Martina, Egberts, Karin, Ehrlich, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Imgart, Hartmut, Scherag, André, Zipfel, Stephan, Boni, Claudette, Ramoz, Nicolas, Versini, Audrey, Danner, Unna N., Hendriks, Judith, Koeleman, Bobby P.C., Ophoff, Roel A., Strengman, Eric, van Elburg, Annemarie A., Bruson, Alice, Clementi, Maurizio, Degortes, Daniela, Forzan, Monica, Tenconi, Elena, Docampo, Elisa, Escaramís, Geòrgia, Jiménez-Murcia, Susana, Lissowska, Jolanta, Rajewski, Andrzej, Szeszenia-Dabrowska, Neonila, Slopien, Agnieszka, Hauser, Joanna, Karhunen, Leila, Meulenbelt, Ingrid, Slagboom, P. Eline, Tortorella, Alfonso, Maj, Mario, Dedoussis, George, DIkeos, DImitris, Gonidakis, Fragiskos, Tziouvas, Konstantinos, Tsitsika, Artemis, Papezova, Hana, Slachtova, Lenka, Martaskova, Debora, Kennedy, James L., Levitan, Robert D., Yilmaz, Zeynep, Huemer, Julia, Koubek, Doris, Merl, Elisabeth, Wagner, Gudrun, Lichtenstein, Paul, Breen, Gerome, Cohen-Woods, Sarah, Farmer, Anne, McGuffin, Peter, Cichon, Sven, Giegling, Ina, Herms, Stefan, Rujescu, Dan, Schreiber, Stefan, Wichmann, H-Erich, Dina, Christian, Sladek, Rob, Gambaro, Giovanni, Soranzo, Nicole, Julia, Antonio, Marsal, Sara, Rabionet, Raquel, Gaborieau, Valerie, DIck, Danielle M., Palotie, Aarno, Ripatti, Samuli, Widén, Elisabeth, Andreassen, Ole A., Espeseth, Thomas, Lundervold, Astri J, Reinvang, Ivar, Steen, Vidar M., Le Hellard, Stephanie, Mattingsdal, Morten, Ntalla, Ioanna, Bencko, Vladimir, Foretova, Lenka, Janout, Vladimir, Navratilova, Marie, Gallinger, Steven, Pinto, Dalila, Scherer, Stephen W., Aschauer, Harald, Carlberg, Laura, Schosser, Alexandra, Alfredsson, Lars, Ding, Bo, Klareskog, Lars, Padyukov, Leonid, Finan, Chris, Kalsi, Gursharan, Roberts, Marion, Barrett, Jeff C., Estivill, Xavier, Hinney, Anke, Sullivan, Patrick F, Zeggini, Eleftheria, Bulik, Cynthia M., Brandt, Harry, Crawford, Steve, Crow, Scott, Fichter, Manfred M., Halmi, Katherine A., Johnson, Craig, Kaplan, Allan S., La Via, Maria C., Mitchell, James R., Strober, Michael, Rotondo, Alessandro, Treasure, Janet, Woodside, D. Blake, Keel, Pamela K., Klump, Kelly L., Lilenfeld, Lisa, Bergen, Andrew W., Kaye, Walter, and Magistretti, Pierre
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- 2017
29. Stage-specific functions of Semaphorin7A during adult hippocampal neurogenesis rely on distinct receptors
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TN groep Ramakers, TN groep Pasterkamp, Brain, Translational Neuroscience 5, Regenerative Medicine and Stem Cells, Jongbloets, Bart C., Lemstra, Suzanne, Schellino, Roberta, Broekhoven, Mark H., Parkash, Jyoti, Hellemons, Anita J C G M, Mao, Tianyi, Giacobini, Paolo, Van Praag, Henriette, De Marchis, Silvia, Ramakers, Geert M J, Pasterkamp, R. Jeroen, TN groep Ramakers, TN groep Pasterkamp, Brain, Translational Neuroscience 5, Regenerative Medicine and Stem Cells, Jongbloets, Bart C., Lemstra, Suzanne, Schellino, Roberta, Broekhoven, Mark H., Parkash, Jyoti, Hellemons, Anita J C G M, Mao, Tianyi, Giacobini, Paolo, Van Praag, Henriette, De Marchis, Silvia, Ramakers, Geert M J, and Pasterkamp, R. Jeroen
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- 2017
30. A new safety index based on intrapulse monitoring of ultra-harmonic cavitation during ultrasound-induced blood-brain barrier opening procedures
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Novell, A., Kamimura, H. A. S., Cafarelli, A., Gerstenmayer, M., Flament, J., Valette, J., Agou, P., Conti, A., Selingue, E., Aron Badin, R., Hantraye, P., Larrat, B., Bodescot, Myriam, Développement et validation d'un dispositif clinique d'ouverture de la barrière hémato-encéphalique par ultrasons focalisés transcraniens - - 3BOPUS2017 - ANR-17-CE19-0025 - AAPG2017 - VALID, Infrastructures - Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences - - NeurATRIS2011 - ANR-11-INBS-0011 - INBS - VALID, Building large instruments for neuroimaging: from population imaging to ultra-high magnetic fields (BAOBAB), Service NEUROSPIN (NEUROSPIN), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neurodegenerative Diseases Laboratory [Fontenay-aux-Roses], Molecular Imaging Research Center [Fontenay-aux-Roses] (MIRCen), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Columbia University [New York], Scuola Universitaria Superiore Sant'Anna [Pisa] (SSSUP), This work is part of the 3BOPUS project, supported by the Agence National de la Recherche (ANR-17-CE19-0025). This study was also supported in part by the European Union (FEDER-2007-2013, agreement #44475), by the Groupement d’intérêt scientifique 'GIS IBiSA', and by the Large National Infrastructure for translational Neuroscience NeurATRIS (ANR-11-INBS-0011)., ANR-17-CE19-0025,3BOPUS,Développement et validation d'un dispositif clinique d'ouverture de la barrière hémato-encéphalique par ultrasons focalisés transcraniens(2017), ANR-11-INBS-0011,NeurATRIS,Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences(2011), Unité Baobab (BAOBAB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire d’imagerie biomédicale multimodale [Orsay] (BioMaps), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)
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Male ,Primates ,Microbubbles ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Ultrasonic Therapy ,lcsh:R ,Settore FIS/07 ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,lcsh:Medicine ,Brain ,Acoustics ,Article ,Rats ,Rats, Sprague-Dawley ,Macaca fascicularis ,Sonication ,Blood-Brain Barrier ,Drug delivery ,Animals ,lcsh:Q ,lcsh:Science ,Biomedical engineering ,Retrospective Studies ,Ultrasonography - Abstract
International audience; Ultrasound-induced blood-brain barrier (BBB) opening using microbubbles is a promising technique for local delivery of therapeutic molecules into the brain. The real-time control of the ultrasound dose delivered through the skull is necessary as the range of pressure for efficient and safe BBB opening is very narrow. Passive cavitation detection (PCD) is a method proposed to monitor the microbubble activity during ultrasound exposure. However, there is still no consensus on a reliable safety indicator able to predict potential damage in the brain. Current approaches for the control of the beam intensity based on PCD employ a full-pulse analysis and may suffer from a lack of sensitivity and poor reaction time. To overcome these limitations, we propose an intra-pulse analysis to monitor the evolution of the frequency content during ultrasound bursts. We hypothesized that the destabilization of microbubbles exposed to a critical level of ultrasound would result in the instantaneous generation of subharmonic and ultra-harmonic components. This specific signature was exploited to define a new sensitive indicator of the safety of the ultrasound protocol. The approach was validated in vivo in rats and non-human primates using a retrospective analysis. Our results demonstrate that intra-pulse monitoring was able to exhibit a sudden appearance of ultra-harmonics during the ultrasound excitation pulse. The repeated detection of such a signature within the excitation pulse was highly correlated with the occurrence of side effects such as hemorrhage and edema. Keeping the acoustic pressure at levels where no such sign of microbubble destabilization occurred resulted in safe BBB openings, as shown by MR images and gross pathology. This new indicator should be more sensitive than conventional full-pulse analysis and can be used to distinguish between potentially harmful and safe ultrasound conditions in the brain with very short reaction time.
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- 2020
31. Molecular composition of skeletal muscle in infants and adults: a comparative proteomic and transcriptomic study.
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Schaiter A, Hentschel A, Kleefeld F, Schuld J, Umathum V, Procida-Kowalski T, Nelke C, Roth A, Hahn A, Krämer HH, Ruck T, Horvath R, van der Ven PFM, Bartkuhn M, Roos A, and Schänzer A
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- Humans, Adult, Middle Aged, Infant, Aged, Male, Female, Young Adult, Tandem Mass Spectrometry, Aging genetics, Aging metabolism, Gene Expression Profiling, Proteome metabolism, Muscle, Skeletal metabolism, Proteomics methods, Transcriptome
- Abstract
To gain a deeper understanding of skeletal muscle function in younger age and aging in elderly, identification of molecular signatures regulating these functions under physiological conditions is needed. Although molecular studies of healthy muscle have been conducted on adults and older subjects, there is a lack of research on infant muscle in terms of combined morphological, transcriptomic and proteomic profiles. To address this gap of knowledge, we performed RNA sequencing (RNA-seq), tandem mass spectrometry (LC-MS/MS), morphometric analysis and assays for mitochondrial maintenance in skeletal muscle biopsies from both, infants aged 4-28 months and adults aged 19-65 years. We identified differently expressed genes (DEGs) and differentially expressed proteins (DEPs) in adults compared to infants. The down-regulated genes in adults were associated with functional terms primarily related to sarcomeres, cellular maintenance, and metabolic, immunological and developmental processes. Thus, our study indicates age-related differences in the molecular signatures and associated functions of healthy skeletal muscle. Moreover, the findings assert that processes previously associated solely with aging are indeed part of development and healthy aging. Hence, combined findings of this study also indicate that age-dependent controls are crucial in muscle disease studies, as otherwise the comparative results may not be reliable., (© 2024. The Author(s).)
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- 2024
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32. Calcium-permeable AMPA receptors govern PV neuron feature selectivity.
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Hong I, Kim J, Hainmueller T, Kim DW, Keijser J, Johnson RC, Park SH, Limjunyawong N, Yang Z, Cheon D, Hwang T, Agarwal A, Cholvin T, Krienen FM, McCarroll SA, Dong X, Leopold DA, Blackshaw S, Sprekeler H, Bergles DE, Bartos M, Brown SP, and Huganir RL
- Abstract
The brain helps us survive by forming internal representations of the external world
1,2 . Excitatory cortical neurons are often precisely tuned to specific external stimuli3,4 . However, inhibitory neurons, such as parvalbumin-positive (PV) interneurons, are generally less selective5 . PV interneurons differ from excitatory neurons in their neurotransmitter receptor subtypes, including AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs)6,7 . Excitatory neurons express calcium-impermeable AMPARs that contain the GluA2 subunit (encoded by GRIA2), whereas PV interneurons express receptors that lack the GluA2 subunit and are calcium-permeable (CP-AMPARs). Here we demonstrate a causal relationship between CP-AMPAR expression and the low feature selectivity of PV interneurons. We find low expression stoichiometry of GRIA2 mRNA relative to other subunits in PV interneurons that is conserved across ferrets, rodents, marmosets and humans, and causes abundant CP-AMPAR expression. Replacing CP-AMPARs in PV interneurons with calcium-impermeable AMPARs increased their orientation selectivity in the visual cortex. Manipulations to induce sparse CP-AMPAR expression demonstrated that this increase was cell-autonomous and could occur with changes beyond development. Notably, excitatory-PV interneuron connectivity rates and unitary synaptic strength were unaltered by CP-AMPAR removal, which suggested that the selectivity of PV interneurons can be altered without markedly changing connectivity. In Gria2-knockout mice, in which all AMPARs are calcium-permeable, excitatory neurons showed significantly degraded orientation selectivity, which suggested that CP-AMPARs are sufficient to drive lower selectivity regardless of cell type. Moreover, hippocampal PV interneurons, which usually exhibit low spatial tuning, became more spatially selective after removing CP-AMPARs, which indicated that CP-AMPARs suppress the feature selectivity of PV interneurons independent of modality. These results reveal a new role of CP-AMPARs in maintaining low-selectivity sensory representation in PV interneurons and implicate a conserved molecular mechanism that distinguishes this cell type in the neocortex., (© 2024. The Author(s).)- Published
- 2024
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33. The International Climate Psychology Collaboration: Climate change-related data collected from 63 countries.
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Doell KC, Todorova B, Vlasceanu M, Bak Coleman JB, Pronizius E, Schumann P, Azevedo F, Patel Y, Berkebile-Wineberg MM, Brick C, Lange F, Grayson SJ, Pei Y, Chakroff A, van den Broek KL, Lamm C, Vlasceanu D, Constantino SM, Rathje S, Goldwert D, Fang K, Aglioti SM, Alfano M, Alvarado-Yepez AJ, Andersen A, Anseel F, Apps MAJ, Asadli C, Awuor FJ, Basaglia P, Bélanger JJ, Berger S, Bertin P, Białek M, Bialobrzeska O, Blaya-Burgo M, Bleize DNM, Bø S, Boecker L, Boggio PS, Borau S, Borau S, Bos B, Bouguettaya A, Brauer M, Brik T, Briker R, Brosch T, Buchel O, Buonauro D, Butalia R, Carvacho H, Chamberlain SAE, Chan HY, Chow D, Chung D, Cian L, Cohen-Eick N, Contreras-Huerta LS, Contu D, Cristea V, Cutler J, D'Ottone S, De Keersmaecker J, Delcourt S, Delouvée S, Diel K, Douglas BD, Drupp MA, Dubey S, Ekmanis J, Elbaek CT, Elsherif M, Engelhard IM, Escher YA, Etienne TW, Farage L, Farias AR, Feuerriegel S, Findor A, Freira L, Friese M, Gains NP, Gallyamova A, Geiger SJ, Genschow O, Gjoneska B, Gkinopoulos T, Goldberg B, Goldenberg A, Gradidge S, Grassini S, Gray K, Grelle S, Griffin SM, Grigoryan L, Grigoryan A, Grigoryev D, Gruber J, Guilaran J, Hadar B, Hahnel UJJ, Halperin E, Harvey AJ, Haugestad CAP, Herman AM, Hershfield HE, Himichi T, Hine DW, Hofmann W, Howe L, Huaman-Chulluncuy ET, Huang G, Ishii T, Ito A, Jia F, Jost JT, Jovanović V, Jurgiel D, Kácha O, Kankaanpää R, Kantorowicz J, Kantorowicz-Reznichenko E, Mintz KK, Kaya I, Kaya O, Khachatryan N, Klas A, Klein C, Klöckner CA, Koppel L, Kosachenko AI, Kothe EJ, Krebs R, Krosch AR, Krouwel APM, Kyrychenko Y, Lagomarsino M, Cunningham JL, Lees J, Leung TY, Levy N, Lockwood PL, Longoni C, Ortega AL, Loschelder DD, Lu JG, Luo Y, Luomba J, Lutz AE, Majer JM, Markowitz E, Marsh AA, Mascarenhas KL, Mbilingi B, Mbungu W, McHugh C, Meijers MHC, Mercier H, Mhagama FL, Michalaki K, Mikus N, Milliron SG, Mitkidis P, Monge-Rodríguez FS, Mora YL, Morais MJ, Moreau D, Motoki K, Moyano M, Mus M, Navajas J, Nguyen TL, Nguyen DM, Nguyen T, Niemi L, Nijssen SRR, Nilsonne G, Nitschke JP, Nockur L, Okura R, Öner S, Özdoğru AA, Palumbo H, Panagopoulos C, Panasiti MS, Pärnamets P, Paruzel-Czachura M, Pavlov YG, Payán-Gómez C, Pearson AR, da Costa LP, Petrowsky HM, Pfattheicher S, Pham NT, Ponizovskiy V, Pretus C, Rêgo GG, Reimann R, Rhoads SA, Riano-Moreno J, Richter I, Röer JP, Rosa-Sullivan J, Ross RM, Sabherwal A, Saito T, Sarrasin O, Say N, Schmid K, Schmitt MT, Schoenegger P, Scholz C, Schug MG, Schulreich S, Shreedhar G, Shuman E, Sivan S, Sjåstad H, Soliman M, Soud K, Spampatti T, Sparkman G, Spasovski O, Stanley SK, Stern JA, Strahm N, Suko Y, Sul S, Syropoulos S, Taylor NC, Tedaldi E, Tinghög G, Huynh LDT, Travaglino GA, Tsakiris M, Tüter İ, Tyrala M, Uluğ ÖM, Urbanek A, Valko D, van der Linden S, van Schie K, van Stekelenburg A, Vanags E, Västfjäll D, Vesely S, Vintr J, Vranka M, Wanguche PO, Willer R, Wojcik AD, Xu R, Yadav A, Zawisza M, Zhao X, Zhao J, Żuk D, and Van Bavel JJ
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- Humans, Surveys and Questionnaires, Climate Change
- Abstract
Climate change is currently one of humanity's greatest threats. To help scholars understand the psychology of climate change, we conducted an online quasi-experimental survey on 59,508 participants from 63 countries (collected between July 2022 and July 2023). In a between-subjects design, we tested 11 interventions designed to promote climate change mitigation across four outcomes: climate change belief, support for climate policies, willingness to share information on social media, and performance on an effortful pro-environmental behavioural task. Participants also reported their demographic information (e.g., age, gender) and several other independent variables (e.g., political orientation, perceptions about the scientific consensus). In the no-intervention control group, we also measured important additional variables, such as environmentalist identity and trust in climate science. We report the collaboration procedure, study design, raw and cleaned data, all survey materials, relevant analysis scripts, and data visualisations. This dataset can be used to further the understanding of psychological, demographic, and national-level factors related to individual-level climate action and how these differ across countries., (© 2024. The Author(s).)
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- 2024
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34. Cognitive performance as a behavioral phenotype associated with cocaine self-administration in female and male socially housed monkeys.
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Allen MI, Costa MB, Johnson BN, Gould RW, and Nader MA
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- Animals, Male, Female, Dopamine Uptake Inhibitors administration & dosage, Dopamine Uptake Inhibitors pharmacology, Cocaine-Related Disorders psychology, Phenotype, Conditioning, Operant drug effects, Behavior, Animal drug effects, Self Administration, Cocaine administration & dosage, Cocaine pharmacology, Macaca fascicularis, Cognition drug effects
- Abstract
Considerable research has suggested that certain cognitive domains may contribute to cocaine misuse. However, there are gaps in the literature regarding whether cognitive performance before drug exposure predicts susceptibility to cocaine self-administration and how cognitive performance relates to future cocaine intake. Thus, the present study aimed to examine cognitive performance, as measured using automated CANTAB cognitive battery, prior to and following acquisition of cocaine self-administration under a concurrent drug vs. food choice procedure in female and male socially housed cynomolgus macaques. The cognitive battery consisted of measures of associative learning (stimulus and compound discrimination tasks), behavioral flexibility (intradimensional and extradimensional tasks), and behavioral inhibition (stimulus discrimination reversal, SDR, and extra-dimensional reversal tasks). After assessing cognitive performance, monkeys were trained to self-administer cocaine (saline, 0.01-0.1 mg/kg/injection) under a concurrent cocaine vs. food schedule of reinforcement. After a history of cocaine self-administration across 3-4 years, the cognitive battery was re-assessed and compared with sensitivity to cocaine reinforcement. Results showed drug-naïve monkeys that were less accurate on the SDR task, measuring behavioral inhibition, were more sensitive to cocaine reinforcement under the concurrent cocaine vs. food choice procedure. Furthermore, following chronic cocaine self-administration, cocaine intake was a negative predictor of accuracy on the SDR behavioral inhibition task. After cocaine maintenance, monkeys with higher cocaine intakes required more trials to complete the SDR behavioral inhibition task and made more incorrect responses during these trials. No sex or social rank differences were noted. Overall, these findings suggest that cognitive performance may influence vulnerability to cocaine misuse. Also, chronic cocaine may decrease levels of behavioral inhibition as measured via the SDR task in both females and males., (© 2024. The Author(s).)
- Published
- 2024
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35. Location and function of TDP-43 in platelets, alterations in neurodegenerative diseases and arising considerations for current plasma biobank protocols.
- Author
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Luthi-Carter R, Cappelli S, Le Roux-Bourdieu M, Tentillier N, Quinn JP, Petrozziello T, Gopalakrishnan L, Sethi P, Choudhary H, Bartolini G, Gebara E, Stuani C, Font L, An J, Ortega V, Sage J, Kosa E, Trombetta BA, Simeone R, Seredenina T, Afroz T, Berry JD, Arnold SE, Carlyle BC, Adolfsson O, Sadri-Vakili G, Buratti E, Bowser R, and Agbas A
- Subjects
- Humans, Amyotrophic Lateral Sclerosis blood, Amyotrophic Lateral Sclerosis metabolism, Amyotrophic Lateral Sclerosis pathology, Biomarkers blood, Cytosol metabolism, Blood Platelets metabolism, DNA-Binding Proteins metabolism, Neurodegenerative Diseases blood, Neurodegenerative Diseases metabolism, Biological Specimen Banks
- Abstract
The TAR DNA Binding Protein 43 (TDP-43) has been implicated in the pathogenesis of human neurodegenerative diseases and exhibits hallmark neuropathology in amyotrophic lateral sclerosis (ALS). Here, we explore its tractability as a plasma biomarker of disease and describe its localization and possible functions in the cytosol of platelets. Novel TDP-43 immunoassays were developed on three different technical platforms and qualified for specificity, signal-to-noise ratio, detection range, variation, spike recovery and dilution linearity in human plasma samples. Surprisingly, implementation of these assays demonstrated that biobank-archived plasma samples yielded considerable heterogeneity in TDP-43 levels. Importantly, subsequent investigation attributed these differences to variable platelet recovery. Fractionations of fresh blood revealed that ≥ 95% of the TDP-43 in platelet-containing plasma was compartmentalized within the platelet cytosol. We reasoned that this highly concentrated source of TDP-43 comprised an interesting substrate for biochemical analyses. Additional characterization of platelets revealed the presence of the disease-associated phosphoserine 409/410 TDP-43 proteoform and many neuron- and astrocyte-expressed TDP-43 mRNA targets. Considering these striking similarities, we propose that TDP-43 may serve analogous functional roles in platelets and synapses, and that the study of platelet TDP-43 might provide a window into disease-related TDP-43 dyshomeostasis in the central nervous system., (© 2024. The Author(s).)
- Published
- 2024
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36. Label-free assessment of complement-dependent cytotoxicity of therapeutic antibodies via a whole-cell MALDI mass spectrometry bioassay.
- Author
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Schmidt S, Geisel A, Enzlein T, Fröhlich BC, Pritchett L, Verneret M, Graf C, and Hopf C
- Subjects
- Humans, Complement System Proteins metabolism, Biological Assay methods, Antibodies, Monoclonal, Glutathione metabolism, Adenosine Triphosphate metabolism, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods, Rituximab pharmacology
- Abstract
Potency assessment of monoclonal antibodies or corresponding biosimilars in cell-based assays is an essential prerequisite in biopharmaceutical research and development. However, cellular bioassays are still subject to limitations in sample throughput, speed, and often need costly reagents or labels as they are based on an indirect readout by luminescence or fluorescence. In contrast, whole-cell Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry (MS) has emerged as a direct, fast and label-free technology for functional drug screening being able to unravel the molecular complexity of cellular response to pharmaceutical reagents. However, this approach has not yet been used for cellular testing of biologicals. In this study, we have conceived, developed and benchmarked a label-free MALDI-MS based cell bioassay workflow for the functional assessment of complement-dependent cytotoxicity (CDC) of Rituximab antibody. By computational evaluation of response profiles followed by subsequent m/z feature annotation via fragmentation analysis and trapped ion mobility MS, we identified adenosine triphosphate and glutathione as readily MS-assessable metabolite markers for CDC and demonstrate that robust concentration-response characteristics can be obtained by MALDI-TOF MS. Statistical assay performance indicators suggest that whole-cell MALDI-TOF MS could complement the toolbox for functional cellular testing of biopharmaceuticals., (© 2024. The Author(s).)
- Published
- 2024
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37. Self-supervised learning of wrist-worn daily living accelerometer data improves the automated detection of gait in older adults.
- Author
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Brand YE, Kluge F, Palmerini L, Paraschiv-Ionescu A, Becker C, Cereatti A, Maetzler W, Sharrack B, Vereijken B, Yarnall AJ, Rochester L, Del Din S, Muller A, Buchman AS, Hausdorff JM, and Perlman O
- Subjects
- Humans, Aged, Male, Female, Aged, 80 and over, Activities of Daily Living, Wrist, Algorithms, Wearable Electronic Devices, Middle Aged, Gait physiology, Accelerometry methods, Accelerometry instrumentation, Supervised Machine Learning
- Abstract
Progressive gait impairment is common among aging adults. Remote phenotyping of gait during daily living has the potential to quantify gait alterations and evaluate the effects of interventions that may prevent disability in the aging population. Here, we developed ElderNet, a self-supervised learning model for gait detection from wrist-worn accelerometer data. Validation involved two diverse cohorts, including over 1000 participants without gait labels, as well as 83 participants with labeled data: older adults with Parkinson's disease, proximal femoral fracture, chronic obstructive pulmonary disease, congestive heart failure, and healthy adults. ElderNet presented high accuracy (96.43 ± 2.27), specificity (98.87 ± 2.15), recall (82.32 ± 11.37), precision (86.69 ± 17.61), and F1 score (82.92 ± 13.39). The suggested method yielded superior performance compared to two state-of-the-art gait detection algorithms, with improved accuracy and F1 score (p < 0.05). In an initial evaluation of construct validity, ElderNet identified differences in estimated daily walking durations across cohorts with different clinical characteristics, such as mobility disability (p < 0.001) and parkinsonism (p < 0.001). The proposed self-supervised method has the potential to serve as a valuable tool for remote phenotyping of gait function during daily living in aging adults, even among those with gait impairments., (© 2024. The Author(s).)
- Published
- 2024
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38. Advancing age and the rs6265 BDNF SNP are permissive to graft-induced dyskinesias in parkinsonian rats.
- Author
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Mercado NM, Szarowicz C, Stancati JA, Sortwell CE, Boezwinkle SA, Collier TJ, Caulfield ME, and Steece-Collier K
- Abstract
The rs6265 single nucleotide polymorphism (SNP) in the gene for brain-derived neurotrophic factor is a common variant that alters therapeutic outcomes for individuals with Parkinson's disease (PD). We previously investigated the effects of this SNP on the experimental therapeutic approach of neural grafting, demonstrating that young adult parkinsonian rats carrying the variant Met allele exhibited enhanced graft function compared to wild-type rats and also exclusively developed aberrant graft-induced dyskinesias (GID). Aging is the primary risk factor for PD and reduces graft efficacy. Here we investigated whether aging interacts with this SNP to further alter cell transplantation outcomes. We hypothesized that aging would reduce enhancement of graft function associated with this genetic variant and exacerbate GID in all grafted subjects. Unexpectedly, beneficial graft function was maintained in aged rs6265 subjects. However, aging was permissive to GID induction, regardless of genotype, with the greatest incidence and severity found in rs6265-expressing animals., (© 2024. The Author(s).)
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- 2024
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39. Psychiatric neuroimaging designs for individualised, cohort, and population studies.
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Gell M, Noble S, Laumann TO, Nelson SM, and Tervo-Clemmens B
- Abstract
Psychiatric neuroimaging faces challenges to rigour and reproducibility that prompt reconsideration of the relative strengths and limitations of study designs. Owing to high resource demands and varying inferential goals, current designs differentially emphasise sample size, measurement breadth, and longitudinal assessments. In this overview and perspective, we provide a guide to the current landscape of psychiatric neuroimaging study designs with respect to this balance of scientific goals and resource constraints. Through a heuristic data cube contrasting key design features, we discuss a resulting trade-off among small sample, precision longitudinal studies (e.g., individualised studies and cohorts) and large sample, minimally longitudinal, population studies. Precision studies support tests of within-person mechanisms, via intervention and tracking of longitudinal course. Population studies support tests of generalisation across multifaceted individual differences. A proposed reciprocal validation model (RVM) aims to recursively leverage these complementary designs in sequence to accumulate evidence, optimise relative strengths, and build towards improved long-term clinical utility., (© 2024. The Author(s).)
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- 2024
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40. Prebiotic diet normalizes aberrant immune and behavioral phenotypes in a mouse model of autism spectrum disorder.
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Prince N, Peralta Marzal LN, Markidi A, Ahmed S, Adolfs Y, Pasterkamp RJ, Kumar H, Roeselers G, Garssen J, Kraneveld AD, and Perez-Pardo P
- Subjects
- Animals, Female, Pregnancy, Mice, Male, Prenatal Exposure Delayed Effects immunology, Brain-Gut Axis drug effects, Brain-Gut Axis physiology, Phenotype, Oligosaccharides administration & dosage, Oligosaccharides pharmacology, Autism Spectrum Disorder immunology, Prebiotics administration & dosage, Mice, Inbred BALB C, Disease Models, Animal, Valproic Acid administration & dosage, Gastrointestinal Microbiome drug effects, Behavior, Animal drug effects
- Abstract
Autism spectrum disorder (ASD) is a cluster of neurodevelopmental disorders characterized by deficits in communication and behavior. Increasing evidence suggests that the microbiota-gut-brain axis and the likely related immune imbalance may play a role in the development of this disorder. Gastrointestinal deficits and gut microbiota dysfunction have been linked to the development or severity of autistic behavior. Therefore, treatments that focus on specific diets may improve gastrointestinal function and aberrant behavior in individuals with ASD. In this study, we investigated whether a diet containing specific prebiotic fibers, namely, 3% galacto-oligosaccharide/fructo-oligosaccharide (GOS/FOS; 9:1), can mitigate the adverse effects of in utero exposure to valproic acid (VPA) in mice. Pregnant BALB/cByJ dams were injected with VPA (600 mg/kg, sc.) or phosphate-buffered saline (PBS) on gestational day 11 (G11). Male offspring were divided into four groups: (1) in utero PBS-exposed with a control diet, (2) in utero PBS-exposed with GOS/FOS diet, (3) in utero VPA-exposed with a control diet, and (4) in utero VPA-exposed with GOS/FOS diet. Dietary intervention started from birth and continued throughout the duration of the experiment. We showed that the prebiotic diet normalized VPA-induced alterations in male offspring, including restoration of key microbial taxa, intestinal permeability, peripheral immune homeostasis, reduction of neuroinflammation in the cerebellum, and impairments in social behavior and cognition in mice. Overall, our research provides valuable insights into the gut-brain axis involvement in ASD development. In addition, dietary interventions might correct the disbalance in gut microbiota and immune responses and, ultimately, might improve detrimental behavioral outcomes in ASD., (© 2024. The Author(s).)
- Published
- 2024
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41. Microglia are dispensable for experience-dependent refinement of mouse visual circuitry.
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Brown TC, Crouse EC, Attaway CA, Oakes DK, Minton SW, Borghuis BG, and McGee AW
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- Animals, Mice, Male, Female, Retina physiology, Visual Pathways physiology, Mice, Inbred C57BL, Neuronal Plasticity physiology, Neurons physiology, Photic Stimulation methods, Mice, Transgenic, Organic Chemicals, Microglia physiology, Visual Cortex physiology, Visual Cortex cytology
- Abstract
To test the hypothesized crucial role of microglia in the developmental refinement of neural circuitry, we depleted microglia from mice of both sexes with PLX5622 and examined the experience-dependent maturation of visual circuitry and function. We assessed retinal function, receptive field tuning of visual cortex neurons, acuity and experience-dependent plasticity. None of these measurements detectibly differed in the absence of microglia, challenging the role of microglia in sculpting neural circuits., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
- Published
- 2024
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42. De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome.
- Author
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Chen Y, Dawes R, Kim HC, Ljungdahl A, Stenton SL, Walker S, Lord J, Lemire G, Martin-Geary AC, Ganesh VS, Ma J, Ellingford JM, Delage E, D'Souza EN, Dong S, Adams DR, Allan K, Bakshi M, Baldwin EE, Berger SI, Bernstein JA, Bhatnagar I, Blair E, Brown NJ, Burrage LC, Chapman K, Coman DJ, Compton AG, Cunningham CA, D'Souza P, Danecek P, Délot EC, Dias KR, Elias ER, Elmslie F, Evans CA, Ewans L, Ezell K, Fraser JL, Gallacher L, Genetti CA, Goriely A, Grant CL, Haack T, Higgs JE, Hinch AG, Hurles ME, Kuechler A, Lachlan KL, Lalani SR, Lecoquierre F, Leitão E, Fevre AL, Leventer RJ, Liebelt JE, Lindsay S, Lockhart PJ, Ma AS, Macnamara EF, Mansour S, Maurer TM, Mendez HR, Metcalfe K, Montgomery SB, Moosajee M, Nassogne MC, Neumann S, O'Donoghue M, O'Leary M, Palmer EE, Pattani N, Phillips J, Pitsava G, Pysar R, Rehm HL, Reuter CM, Revencu N, Riess A, Rius R, Rodan L, Roscioli T, Rosenfeld JA, Sachdev R, Shaw-Smith CJ, Simons C, Sisodiya SM, Snell P, St Clair L, Stark Z, Stewart HS, Tan TY, Tan NB, Temple SEL, Thorburn DR, Tifft CJ, Uebergang E, VanNoy GE, Vasudevan P, Vilain E, Viskochil DH, Wedd L, Wheeler MT, White SM, Wojcik M, Wolfe LA, Wolfenson Z, Wright CF, Xiao C, Zocche D, Rubenstein JL, Markenscoff-Papadimitriou E, Fica SM, Baralle D, Depienne C, MacArthur DG, Howson JMM, Sanders SJ, O'Donnell-Luria A, and Whiffin N
- Subjects
- Adolescent, Child, Child, Preschool, Female, Humans, Infant, Male, Young Adult, Alleles, Brain growth & development, Brain metabolism, Heterozygote, RNA Splice Sites genetics, Spliceosomes genetics, Syndrome, Rare Diseases genetics, Gene Expression Regulation, Developmental, Mutation, Neurodevelopmental Disorders genetics, RNA, Small Nuclear genetics
- Abstract
Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes
1 . Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2 . We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals in whom it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologues. Using RNA sequencing, we show how 5' splice-site use is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 base pair region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide., (© 2024. The Author(s).)- Published
- 2024
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43. TMEFF1 is a neuron-specific restriction factor for herpes simplex virus.
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Dai Y, Idorn M, Serrero MC, Pan X, Thomsen EA, Narita R, Maimaitili M, Qian X, Iversen MB, Reinert LS, Flygaard RK, Chen M, Ding X, Zhang BC, Carter-Timofte ME, Lu Q, Jiang Z, Zhong Y, Zhang S, Da L, Zhu J, Denham M, Nissen P, Mogensen TH, Mikkelsen JG, Zhang SY, Casanova JL, Cai Y, and Paludan SR
- Subjects
- Animals, Female, Humans, Male, Mice, Cell Death, CRISPR-Cas Systems genetics, Viral Load, Nectins metabolism, Nonmuscle Myosin Type IIA metabolism, Nonmuscle Myosin Type IIB metabolism, Interferon Type I, Neuroinflammatory Diseases immunology, Neuroinflammatory Diseases metabolism, Neuroinflammatory Diseases pathology, Neuroinflammatory Diseases prevention & control, Neuroinflammatory Diseases virology, Antiviral Restriction Factors metabolism, Brain cytology, Brain metabolism, Brain pathology, Brain virology, Herpes Simplex immunology, Herpes Simplex metabolism, Herpes Simplex virology, Herpesvirus 1, Human growth & development, Herpesvirus 1, Human immunology, Herpesvirus 1, Human physiology, Membrane Proteins metabolism, Membrane Proteins deficiency, Membrane Proteins genetics, Neurons virology, Neurons metabolism, Virus Internalization, Virus Replication
- Abstract
The brain is highly sensitive to damage caused by infection and inflammation
1,2 . Herpes simplex virus 1 (HSV-1) is a neurotropic virus and the cause of herpes simplex encephalitis3 . It is unknown whether neuron-specific antiviral factors control virus replication to prevent infection and excessive inflammatory responses, hence protecting the brain. Here we identify TMEFF1 as an HSV-1 restriction factor using genome-wide CRISPR screening. TMEFF1 is expressed specifically in neurons of the central nervous system and is not regulated by type I interferon, the best-known innate antiviral system controlling virus infections. Depletion of TMEFF1 in stem-cell-derived human neurons led to elevated viral replication and neuronal death following HSV-1 infection. TMEFF1 blocked the HSV-1 replication cycle at the level of viral entry through interactions with nectin-1 and non-muscle myosin heavy chains IIA and IIB, which are core proteins in virus-cell binding and virus-cell fusion, respectively4-6 . Notably, Tmeff1-/- mice exhibited increased susceptibility to HSV-1 infection in the brain but not in the periphery. Within the brain, elevated viral load was observed specifically in neurons. Our study identifies TMEFF1 as a neuron-specific restriction factor essential for prevention of HSV-1 replication in the central nervous system., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2024
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44. Single-cell atlas of the human brain vasculature across development, adulthood and disease.
- Author
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Wälchli T, Ghobrial M, Schwab M, Takada S, Zhong H, Suntharalingham S, Vetiska S, Gonzalez DR, Wu R, Rehrauer H, Dinesh A, Yu K, Chen ELY, Bisschop J, Farnhammer F, Mansur A, Kalucka J, Tirosh I, Regli L, Schaller K, Frei K, Ketela T, Bernstein M, Kongkham P, Carmeliet P, Valiante T, Dirks PB, Suva ML, Zadeh G, Tabar V, Schlapbach R, Jackson HW, De Bock K, Fish JE, Monnier PP, Bader GD, and Radovanovic I
- Subjects
- Female, Humans, Male, Cell Communication, HLA-D Antigens metabolism, Adult, Health, Brain blood supply, Brain pathology, Brain embryology, Brain metabolism, Brain Neoplasms blood supply, Brain Neoplasms pathology, Endothelial Cells metabolism, Endothelial Cells pathology, Endothelial Cells cytology, Fetus blood supply, Fetus cytology, Fetus embryology, RNA-Seq, Single-Cell Gene Expression Analysis, Central Nervous System Vascular Malformations pathology
- Abstract
A broad range of brain pathologies critically relies on the vasculature, and cerebrovascular disease is a leading cause of death worldwide. However, the cellular and molecular architecture of the human brain vasculature remains incompletely understood
1 . Here we performed single-cell RNA sequencing analysis of 606,380 freshly isolated endothelial cells, perivascular cells and other tissue-derived cells from 117 samples, from 68 human fetuses and adult patients to construct a molecular atlas of the developing fetal, adult control and diseased human brain vasculature. We identify extensive molecular heterogeneity of the vasculature of healthy fetal and adult human brains and across five vascular-dependent central nervous system (CNS) pathologies, including brain tumours and brain vascular malformations. We identify alteration of arteriovenous differentiation and reactivated fetal as well as conserved dysregulated genes and pathways in the diseased vasculature. Pathological endothelial cells display a loss of CNS-specific properties and reveal an upregulation of MHC class II molecules, indicating atypical features of CNS endothelial cells. Cell-cell interaction analyses predict substantial endothelial-to-perivascular cell ligand-receptor cross-talk, including immune-related and angiogenic pathways, thereby revealing a central role for the endothelium within brain neurovascular unit signalling networks. Our single-cell brain atlas provides insights into the molecular architecture and heterogeneity of the developing, adult/control and diseased human brain vasculature and serves as a powerful reference for future studies., (© 2024. Crown.)- Published
- 2024
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45. Parvalbumin interneuron mGlu 5 receptors govern sex differences in prefrontal cortex physiology and binge drinking.
- Author
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Fabian CB, Jordan ND, Cole RH, Carley LG, Thompson SM, Seney ML, and Joffe ME
- Subjects
- Animals, Male, Female, Mice, Receptors, Metabotropic Glutamate metabolism, Receptors, Metabotropic Glutamate genetics, Endocannabinoids metabolism, Ethanol pharmacology, Ethanol administration & dosage, Prefrontal Cortex metabolism, Prefrontal Cortex drug effects, Parvalbumins metabolism, Interneurons metabolism, Interneurons physiology, Interneurons drug effects, Sex Characteristics, Binge Drinking metabolism, Binge Drinking physiopathology, Receptor, Metabotropic Glutamate 5 metabolism, Mice, Inbred C57BL
- Abstract
Despite established sex differences in the prevalence and presentation of psychiatric disorders, little is known about the cellular and synaptic mechanisms that guide these differences under basal conditions. The proper function of the prefrontal cortex (PFC) is essential for the top-down regulation of motivated behaviors. The activity of the PFC is tightly controlled by parvalbumin-expressing interneurons (PV-INs), a key subpopulation of fast-spiking GABAergic cells that regulate cortical excitability through direct innervations onto the perisomatic regions of nearby pyramidal cells. Recent rodent studies have identified notable sex differences in PV-IN activity and adaptations to experiences such as binge drinking. Here, we investigated the cellular and molecular mechanisms that underlie sex-specific regulation of PFC PV-IN function. Using whole-cell patch-clamp electrophysiology and selective pharmacology, we report that PV-INs from female mice are more excitable than those from males. Moreover, we find that mGlu
1 and mGlu5 metabotropic glutamate receptors regulate cell excitability, excitatory drive, and endocannabinoid signaling at PFC PV-INs in a sex-dependent manner. Genetic deletion of mGlu5 receptors from PV-expressing cells abrogates all sex differences observed in PV-IN membrane and synaptic physiology. Lastly, we report that female, but not male, PV-mGlu5 -/ - mice exhibit decreased voluntary drinking on an intermittent access schedule, which could be related to changes in ethanol's stimulant properties. Importantly, these studies identify mGlu1 and mGlu5 receptors as candidate signaling molecules involved in sex differences in PV-IN activity and behaviors relevant to alcohol use., (© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)- Published
- 2024
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46. Harnessing the frontal aslant tract's structure to assess its involvement in cognitive functions: new insights from 7-T diffusion imaging.
- Author
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Serrano-Sponton L, Lange F, Dauth A, Krenzlin H, Perez A, Januschek E, Schumann S, Jussen D, Czabanka M, Ringel F, Keric N, and Gonzalez-Escamilla G
- Subjects
- Humans, Male, Female, Adult, Diffusion Magnetic Resonance Imaging methods, Middle Aged, Young Adult, Glioma diagnostic imaging, Glioma surgery, Glioma pathology, Dorsolateral Prefrontal Cortex diagnostic imaging, Cognition physiology, Diffusion Tensor Imaging methods
- Abstract
The first therapeutical goal followed by neurooncological surgeons dealing with prefrontal gliomas is attempting supramarginal tumor resection preserving relevant neurological function. Therefore, advanced knowledge of the frontal aslant tract (FAT) functional neuroanatomy in high-order cognitive domains beyond language and speech processing would help refine neurosurgeries, predicting possible relevant cognitive adverse events and maximizing the surgical efficacy. To this aim we performed the recently developed correlational tractography analyses to evaluate the possible relationship between FAT's microstructural properties and cognitive functions in 27 healthy subjects having ultra-high-field (7-Tesla) diffusion MRI. We independently assessed FAT segments innervating the dorsolateral prefrontal cortices (dlPFC-FAT) and the supplementary motor area (SMA-FAT). FAT microstructural robustness, measured by the tract's quantitative anisotropy (QA), was associated with a better performance in episodic memory, visuospatial orientation, cognitive processing speed and fluid intelligence but not sustained selective attention tests. Overall, the percentual tract volume showing an association between QA-index and improved cognitive scores (pQACV) was higher in the SMA-FAT compared to the dlPFC-FAT segment. This effect was right-lateralized for verbal episodic memory and fluid intelligence and bilateralized for visuospatial orientation and cognitive processing speed. Our results provide novel evidence for a functional specialization of the FAT beyond the known in language and speech processing, particularly its involvement in several higher-order cognitive domains. In light of these findings, further research should be encouraged to focus on neurocognitive deficits and their impact on patient outcomes after FAT damage, especially in the context of glioma surgery., (© 2024. The Author(s).)
- Published
- 2024
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47. Human tripartite cortical network model for temporal assessment of alpha-synuclein aggregation and propagation in Parkinson's Disease.
- Author
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Kapucu FE, Tujula I, Kulta O, Sukki L, Ryynänen T, Gram H, Vuolanto V, Vinogradov A, Kreutzer J, Jensen PH, Kallio P, and Narkilahti S
- Abstract
Previous studies have shown that aggregated alpha-synuclein (α-s) protein, a key pathological marker of Parkinson's disease (PD), can propagate between cells, thus participating in disease progression. This prion-like propagation has been widely studied using in vivo and in vitro models, including rodent and human cell cultures. In this study, our focus was on temporal assessment of functional changes during α-s aggregation and propagation in human induced pluripotent stem cell (hiPSC)-derived neuronal cultures and in engineered networks. Here, we report an engineered circular tripartite human neuronal network model in a microfluidic chip integrated with microelectrode arrays (MEAs) as a platform to study functional markers during α-s aggregation and propagation. We observed progressive aggregation of α-s in conventional neuronal cultures and in the exposed (proximal) compartments of circular tripartite networks following exposure to preformed α-s fibrils (PFF). Furthermore, aggregated forms propagated to distal compartments of the circular tripartite networks through axonal transport. We observed impacts of α-s aggregation on both the structure and function of neuronal cells, such as in presynaptic proteins, mitochondrial motility, calcium oscillations and neuronal activity. The model enabled an assessment of the early, middle, and late phases of α-s aggregation and its propagation during a 13-day follow-up period. While our temporal analysis suggested a complex interplay of structural and functional changes during the in vitro propagation of α-s aggregates, further investigation is required to elucidate the underlying mechanisms. Taken together, this study demonstrates the technical potential of our introduced model for conducting in-depth analyses for revealing such mechanisms., (© 2024. The Author(s).)
- Published
- 2024
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48. Human neuroimaging and antipsychotic neurobiology at millisecond temporal resolution.
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Eisenberg DP and Berman KF
- Published
- 2024
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49. Cumulative lifetime stressor exposure impairs stimulus-response but not contextual learning.
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Rosero-Pahi M, Andoh J, Shields GS, Acosta-Ortiz A, Serrano-Gomez S, and Slavich GM
- Subjects
- Humans, Male, Female, Adult, Middle Aged, Young Adult, Hippocampus physiology, Corpus Striatum physiology, Stress, Psychological physiopathology, Learning physiology
- Abstract
Greater exposure to stressors over the life course is believed to promote striatum-dependent over hippocampus-dependent learning and memory processes under stressful conditions. However, little research in this context has actually assessed lifetime stressor exposure and, moreover, it remains unknown whether greater cumulative lifetime stressor exposure exerts comparable effects on striatum-dependent learning and hippocampus-dependent learning in non-stressful contexts. To investigate this issue, we used the Stress and Adversity Inventory for Adults (Adult STRAIN) and Multicued Search Task to investigate the relation between cumulative lifetime stressor exposure and striatum-dependent stimulus-response learning and hippocampus-dependent contextual learning under non-stressful conditions among healthcare professionals (N = 205; 157 females, 48 males; Age: M = 34.23, SD 9.3, range 20-59 years). Individuals with moderate, but not low, cumulative lifetime stressor exposure exhibited impaired learning for stimulus-response associations. In contrast, learning for context associations was unrelated to participants' lifetime stressor exposure profiles. These results thus provide first evidence that cumulative lifetime stressor exposure may have negative consequences on human striatum-dependent stimulus-response learning under non-stressful environmental conditions., (© 2024. The Author(s).)
- Published
- 2024
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50. Altered excitatory and inhibitory ionotropic receptor subunit expression in the cortical visuospatial working memory network in schizophrenia.
- Author
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Schoonover KE, Dienel SJ, Holly Bazmi H, Enwright JF 3rd, and Lewis DA
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Receptors, AMPA metabolism, Receptors, AMPA genetics, Receptors, GABA-A metabolism, Receptors, GABA-A genetics, Receptors, GABA-A biosynthesis, Aged, RNA, Messenger metabolism, Schizophrenia metabolism, Schizophrenia physiopathology, Schizophrenia genetics, Memory, Short-Term physiology, Receptors, N-Methyl-D-Aspartate metabolism, Receptors, N-Methyl-D-Aspartate genetics
- Abstract
Dysfunction of the cortical dorsal visual stream and visuospatial working memory (vsWM) network in individuals with schizophrenia (SZ) likely reflects alterations in both excitatory and inhibitory neurotransmission within nodes responsible for information transfer across the network, including primary visual (V1), visual association (V2), posterior parietal (PPC), and dorsolateral prefrontal (DLPFC) cortices. However, the expression patterns of ionotropic glutamatergic and GABAergic receptor subunits across these regions, and alterations of these patterns in SZ, have not been investigated. We quantified transcript levels of key subunits for excitatory N-methyl-D-aspartate receptors (NMDARs), excitatory alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs), and inhibitory GABA
A receptors (GABAARs) in postmortem total gray matter from V1, V2, PPC, and DLPFC of unaffected comparison (UC) and matched SZ subjects. In UC subjects, levels of most AMPAR and NMDAR mRNAs exhibited opposite rostral-to-caudal gradients, with AMPAR GRIA1 and GRIA2 mRNA levels highest in DLPFC and NMDAR GRIN1 and GRIN2A mRNA levels highest in V1. GABRA5 and GABRA1 mRNA levels were highest in DLPFC and V1, respectively. In SZ, most transcript levels were lower relative to UC subjects, with these differences largest in V1, intermediate in V2 and PPC, and smallest in DLPFC. In UC subjects, these distinct patterns of receptor transcript levels across the cortical vsWM network suggest that the balance between excitation and inhibition is achieved in a region-specific manner. In SZ subjects, the large deficits in excitatory and inhibitory receptor transcript levels in caudal sensory regions suggest that abnormalities early in the vsWM pathway might contribute to altered information processing in rostral higher-order regions., (© 2024. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)- Published
- 2024
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