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1,147 results on '"Neve, Rachael L."'

4. Comparative Transcriptional Analyses in the Nucleus Accumbens Identifies RGS2 as a Key Mediator of Depression-Related Behavior

Author

Williams, Alexia V, Peña, Catherine J, Ramos-Maciel, Stephanie, Laman-Maharg, Abigail, Ordoñez-Sanchez, Evelyn, Britton, Monica, Durbin-Johnson, Blythe, Settles, Matt, Hao, Rebecca, Yokoyama, Sae, Xu, Christine, Luo, Pei X, Dwyer, Tjien, Bhela, Shanu, Black, Alexis M, Labonté, Benoit, Serafini, Randal Alex, Ruiz, Anne, Neve, Rachael L, Zachariou, Venetia, Nestler, Eric J, and Trainor, Brian C

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Basic Behavioral and Social Science, Depression, Mental Illness, Behavioral and Social Science, Mental Health, Brain Disorders, Neurosciences, Major Depressive Disorder, Mental health, Good Health and Well Being, Animals, Female, Male, Mice, Nucleus Accumbens, Depressive Disorder, Major, Stress, Psychological, Disease Models, Animal, Behavior, Animal, Social Behavior, Mice, Inbred C57BL, Major depression, Nucleus accumbens, Peromyscus californicus, Prefrontal cortex, Reward, Social defeat, Ventral tegmental area, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences
Abstract

BackgroundMajor depressive disorder is one of the most commonly diagnosed mental illnesses worldwide, with a higher prevalence in women than in men. Although currently available pharmacological therapeutics help many individuals, they are not effective for most. Animal models have been important for the discovery of molecular alterations in stress and depression, but difficulties in adapting animal models of depression for females has impeded progress in developing novel therapeutic treatments that may be more efficacious for women.MethodsUsing the California mouse social defeat model, we took a multidisciplinary approach to identify stress-sensitive molecular targets that have translational relevance for women. We determined the impact of stress on transcriptional profiles in male and female California mouse nucleus accumbens (NAc) and compared these results with data from postmortem samples of the NAc from men and women diagnosed with major depressive disorder.ResultsOur cross-species computational analyses identified Rgs2 (regulator of G protein signaling 2) as a transcript downregulated by social defeat stress in female California mice and in women with major depressive disorder. RGS2 plays a key role in signal regulation of neuropeptide and neurotransmitter receptors. Viral vector-mediated overexpression of Rgs2 in the NAc restored social approach and sucrose preference in stressed female California mice.ConclusionsThese studies show that Rgs2 acting in the NAc has functional properties that translate to changes in anxiety- and depression-related behavior. Future studies should investigate whether targeting Rgs2 represents a novel target for treatment-resistant depression in women.

Published
2022

5. A basomedial amygdala to intercalated cells microcircuit expressing PACAP and its receptor PAC1 regulates contextual fear

Author

Rajbhandari, Abha K, Octeau, Christopher J, Gonzalez, Sarah, Pennington, Zachary T, Mohamed, Farzanna, Trott, Jeremy, Chavez, Jasmine, Ngyuen, Erin, Keces, Natasha, Hong, Weizhe Z, Neve, Rachael L, Waschek, James, Khakh, Baljit S, and Fanselow, Michael S

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Post-Traumatic Stress Disorder (PTSD), Anxiety Disorders, Neurosciences, Mental Health, Behavioral and Social Science, Brain Disorders, 1.1 Normal biological development and functioning, Underpinning research, Amygdala, Animals, Excitatory Postsynaptic Potentials, Extinction, Psychological, Fear, Female, Male, Mice, Mice, Inbred C57BL, Neurons, Optogenetics, Pituitary Adenylate Cyclase-Activating Polypeptide, Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I, Sex Factors, Stress Disorders, Post-Traumatic, amygdala, fear, PACAP, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

Trauma can cause dysfunctional fear regulation leading some people to develop disorders, such as post-traumatic stress disorder (PTSD). The amygdala regulates fear, whereas PACAP (pituitary adenylate activating peptide) and PAC1 receptors are linked to PTSD symptom severity at genetic/epigenetic levels, with a strong link in females with PTSD. We discovered a PACAPergic projection from the basomedial amygdala (BMA) to the medial intercalated cells (mICCs) in adult mice. In vivo optogenetic stimulation of this pathway increased CFOS expression in mICCs, decreased fear recall, and increased fear extinction. Selective deletion of PAC1 receptors from the mICCs in females reduced fear acquisition, but enhanced fear generalization and reduced fear extinction in males. Optogenetic stimulation of the BMA-mICC PACAPergic pathway produced EPSCs in mICC neurons, which were enhanced by the PAC1 receptor antagonist, PACAP 6-38. Our findings show that mICCs modulate contextual fear in a dynamic and sex-dependent manner via a microcircuit containing the BMA and mICCs, and in a manner that was dependent on behavioral state.SIGNIFICANCE STATEMENT Traumatic stress can affect different aspects of fear behaviors, including fear learning, generalization of learned fear to novel contexts, how the fear of the original context is recalled, and how fear is reduced over time. While the amygdala has been studied for its role in regulation of different aspects of fear, the molecular circuitry of this structure is quite complex. In addition, aspects of fear can be modulated differently in males and females. Our findings show that a specific circuitry containing the neuropeptide PACAP and its receptor, PAC1, regulates various aspects of fear, including acquisition, generalization, recall, and extinction in a sexually dimorphic manner, characterizing a novel pathway that modulates traumatic fear.

Published
2021

7. CREB Binding at the Zfp189 Promoter Within Medium Spiny Neuron Subtypes Differentially Regulates Behavioral and Physiological Adaptations Over the Course of Cocaine Use

Author

Teague, Collin D., Picone, Joseph A., Wright, William J., Browne, Caleb J., Silva, Gabriella M., Futamura, Rita, Minier-Toribio, Angélica, Estill, Molly E., Ramakrishnan, Aarthi, Martinez-Rivera, Freddyson J., Godino, Arthur, Parise, Eric M., Schmidt, Kyra H., Pulido, Nathalia V., Lorsch, Zachary S., Kim, Jee Hyun, Shen, Li, Neve, Rachael L., Dong, Yan, Nestler, Eric J., and Hamilton, Peter J.

Published
2023
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8. Rescue of deficits by Brwd1 copy number restoration in the Ts65Dn mouse model of Down syndrome

Author

Fulton, Sasha L., Wenderski, Wendy, Lepack, Ashley E., Eagle, Andrew L., Fanutza, Tomas, Bastle, Ryan M., Ramakrishnan, Aarthi, Hays, Emma C., Neal, Arianna, Bendl, Jaroslav, Farrelly, Lorna A., Al-Kachak, Amni, Lyu, Yang, Cetin, Bulent, Chan, Jennifer C., Tran, Tina N., Neve, Rachael L., Roper, Randall J., Brennand, Kristen J., Roussos, Panos, Schimenti, John C., Friedman, Allyson K., Shen, Li, Blitzer, Robert D., Robison, Alfred J., Crabtree, Gerald R., and Maze, Ian

Published
2022
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13. Regulation of impulsive and aggressive behaviours by a novel lncRNA

Author

Labonté, Benoit, Abdallah, Khaled, Maussion, Gilles, Yerko, Volodymyr, Yang, Jennie, Bittar, Thibault, Quessy, Francis, Golden, Sam A., Navarro, Luis, Checknita, Dave, Gigek, Carolina, Lopez, Juan Pablo, Neve, Rachael L., Russo, Scott J., Tremblay, Richard E., Côté, Gilles, Meaney, Michael J., Mechawar, Naguib, Nestler, Eric J., and Turecki, Gustavo

Published
2021
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15. Sex-Specific Role for the Long Non-coding RNA LINC00473 in Depression

Author

Issler, Orna, van der Zee, Yentl Y., Ramakrishnan, Aarthi, Wang, Junshi, Tan, Chunfeng, Loh, Yong-Hwee E., Purushothaman, Immanuel, Walker, Deena M., Lorsch, Zachary S., Hamilton, Peter J., Peña, Catherine J., Flaherty, Erin, Hartley, Brigham J., Torres-Berrío, Angélica, Parise, Eric M., Kronman, Hope, Duffy, Julia E., Estill, Molly S., Calipari, Erin S., Labonté, Benoit, Neve, Rachael L., Tamminga, Carol A., Brennand, Kristen J., Dong, Yan, Shen, Li, and Nestler, Eric J.

Published
2020
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16. Periodic Remodeling in a Neural Circuit Governs Timing of Female Sexual Behavior

Author

Inoue, Sayaka, primary, Yang, Renzhi, additional, Tantry, Adarsh, additional, Davis, Chung-ha, additional, Yang, Taehong, additional, Knoedler, Joseph R., additional, Wei, Yichao, additional, Adams, Eliza L., additional, Thombare, Shivani, additional, Golf, Samantha R., additional, Neve, Rachael L., additional, Tessier-Lavigne, Marc, additional, Ding, Jun B., additional, and Shah, Nirao M., additional

Published
2024
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18. Revision of Alzheimer's diagnostic criteria or relocation of the Potemkin village

Author

Høilund-Carlsen, Poul F., Alavi, Abass, Barrio, Jorge R., Castellani, Rudolph J., Costa, Tommaso, Herrup, Karl, Kepp, Kasper P., Neve, Rachael L., Perry, George, Revheim, Mona Elisabeth, Robakis, Nikolaos K., Sensi, Stefano L., Vissel, Bryce, Høilund-Carlsen, Poul F., Alavi, Abass, Barrio, Jorge R., Castellani, Rudolph J., Costa, Tommaso, Herrup, Karl, Kepp, Kasper P., Neve, Rachael L., Perry, George, Revheim, Mona Elisabeth, Robakis, Nikolaos K., Sensi, Stefano L., and Vissel, Bryce

Abstract

The recently announced revision of the Alzheimer's disease (AD) diagnostic ATN classification adds to an already existing disregard for clinical assessment the rejection of image-based in vivo assessment of the brain's condition. The revision suggests that the diagnosis of AD should be based solely on the presence of cerebral amyloid-beta and tau, indicated by the “A” and "T". The "N", which stands for neurodegeneration – detected by imaging – should no longer be given importance, except that A+ ± T + = AD with amyloid PET being the main method for demonstrating A+. We believe this is an artificial and misleading suggestion. It is artificial because it relies on biomarkers whose significance remains obscure and where the detection of “A” is based on a never-validated PET method using a tracer that marks much more than amyloid-beta. It is misleading because many patients without dementia will be falsely classified as having AD, but nonetheless candidates for passive immunotherapy, which may be more harmful than beneficial, and sometimes fatal.

Published
2024

19. Alzheimer’s Amyloid Hypothesis and Antibody Therapy: Melting Glaciers?

Author

Høilund-Carlsen, Poul F., Alavi, Abass, Castellani, Rudolph J., Neve, Rachael L., Perry, George, Revheim, Mona-Elisabeth, Barrio, Jorge R., Høilund-Carlsen, Poul F., Alavi, Abass, Castellani, Rudolph J., Neve, Rachael L., Perry, George, Revheim, Mona-Elisabeth, and Barrio, Jorge R.

Abstract

The amyloid cascade hypothesis for Alzheimer’s disease is still alive, although heavily challenged. Effective anti-amyloid immunotherapy would confirm the hypothesis’ claim that the protein amyloid-beta is the cause of the disease. Two antibodies, aducanumab and lecanemab, have been approved by the U.S. Food and Drug Administration, while a third, donanemab, is under review. The main argument for the FDA approvals is a presumed therapy-induced removal of cerebral amyloid deposits. Lecanemab and donanemab are also thought to cause some statistical delay in the determination of cognitive decline. However, clinical efficacy that is less than with conventional treatment, selection of amyloid-positive trial patients with non-specific amyloid-PET imaging, and uncertain therapy-induced removal of cerebral amyloids in clinical trials cast doubt on this anti-Alzheimer’s antibody therapy and hence on the amyloid hypothesis, calling for a more thorough investigation of the negative impact of this type of therapy on the brain.

Published
2024

22. G9a influences neuronal subtype specification in striatum

Author

Maze, Ian, Chaudhury, Dipesh, Dietz, David M, Von Schimmelmann, Melanie, Kennedy, Pamela J, Lobo, Mary Kay, Sillivan, Stephanie E, Miller, Michael L, Bagot, Rosemary C, Sun, HaoSheng, Turecki, Gustavo, Neve, Rachael L, Hurd, Yasmin L, Shen, Li, Han, Ming-Hu, Schaefer, Anne, and Nestler, Eric J

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Drug Abuse (NIDA only), Substance Misuse, Brain Disorders, Genetics, Neurosciences, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Adolescent, Adult, Aged, Animals, Cocaine, Corpus Striatum, Dopaminergic Neurons, Female, Histone-Lysine N-Methyltransferase, Humans, Male, Mice, Middle Aged, Organ Specificity, Receptors, Dopamine D1, Receptors, Dopamine D2, Young Adult, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Cocaine-mediated repression of the histone methyltransferase (HMT) G9a has recently been implicated in transcriptional, morphological and behavioral responses to chronic cocaine administration. Here, using a ribosomal affinity purification approach, we found that G9a repression by cocaine occurred in both Drd1-expressing (striatonigral) and Drd2-expressing (striatopallidal) medium spiny neurons. Conditional knockout and overexpression of G9a within these distinct cell types, however, revealed divergent behavioral phenotypes in response to repeated cocaine treatment. Our studies further indicated that such developmental deletion of G9a selectively in Drd2 neurons resulted in the unsilencing of transcriptional programs normally specific to striatonigral neurons and in the acquisition of Drd1-associated projection and electrophysiological properties. This partial striatopallidal to striatonigral 'switching' phenotype in mice indicates a new role for G9a in contributing to neuronal subtype identity and suggests a critical function for cell type-specific histone methylation patterns in the regulation of behavioral responses to environmental stimuli.

Published
2014

26. Stress resilience is promoted by a Zfp189-driven transcriptional network in prefrontal cortex

Author

Lorsch, Zachary S., Hamilton, Peter J., Ramakrishnan, Aarthi, Parise, Eric M., Salery, Marine, Wright, William J., Lepack, Ashley E., Mews, Philipp, Issler, Orna, McKenzie, Andrew, Zhou, Xianxiao, Parise, Lyonna F., Pirpinias, Stephen T., Ortiz Torres, Idelisse, Kronman, Hope G., Montgomery, Sarah E., Loh, Yong-Hwee Eddie, Labonté, Benoit, Conkey, Andrew, Symonds, Ann E., Neve, Rachael L., Turecki, Gustavo, Maze, Ian, Dong, Yan, Zhang, Bin, Shen, Li, Bagot, Rosemary C., and Nestler, Eric J.

Published
2019
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28. Association between regulator of G protein signaling 9-2 and body weight.

Author

Waugh, Jeffrey L, Celver, Jeremy, Sharma, Meenakshi, Dufresne, Robert L, Terzi, Dimitra, Risch, S Craig, Fairbrother, William G, Neve, Rachael L, Kane, John P, Malloy, Mary J, Pullinger, Clive R, Gu, Harvest F, Tsatsanis, Christos, Hamilton, Steven P, Gold, Stephen J, Zachariou, Venetia, and Kovoor, Abraham

Subjects
Nucleus Accumbens, Adipose Tissue, Adipocytes, Animals, Mice, Knockout, Humans, Mice, Rats, Body Weight, Weight Loss, RGS Proteins, Body Mass Index, Motor Activity, RNA Splicing, Sequence Deletion, Base Sequence, Genes, Reporter, Introns, Molecular Sequence Data, Female, Male, Intra-Abdominal Fat, Genetic Association Studies, Genes, Reporter, Knockout, General Science & Technology
Abstract

Regulator of G protein signaling 9-2 (RGS9-2) is a protein that is highly enriched in the striatum, a brain region that mediates motivation, movement and reward responses. We identified a naturally occurring 5 nucleotide deletion polymorphism in the human RGS9 gene and found that the mean body mass index (BMI) of individuals with the deletion was significantly higher than those without. A splicing reporter minigene assay demonstrated that the deletion had the potential to significantly decrease the levels of correctly spliced RGS9 gene product. We measured the weights of rats after virally transduced overexpression of RGS9-2 or the structurally related RGS proteins, RGS7, or RGS11, in the nucleus accumbens (NAc) and observed a reduction in body weight after overexpression of RGS9-2 but not RGS7 or 11. Conversely, we found that the RGS9 knockout mice were heavier than their wild-type littermates and had significantly higher percentages of abdominal fat. The constituent adipocytes were found to have a mean cross-sectional area that was more than double that of corresponding cells from wild-type mice. However, food intake and locomotion were not significantly different between the two strains. These studies with humans, rats and mice implicate RGS9-2 as a factor in regulating body weight.

Published
2011

31. Dnmt3a regulates emotional behavior and spine plasticity in the nucleus accumbens

Author

LaPlant, Quincey, Vialou, Vincent, Covington, Herbert E, Dumitriu, Dani, Feng, Jian, Warren, Brandon L, Maze, Ian, Dietz, David M, Watts, Emily L, Iñiguez, Sergio D, Koo, Ja Wook, Mouzon, Ezekiell, Renthal, William, Hollis, Fiona, Wang, Hui, Noonan, Michele A, Ren, Yanhua, Eisch, Amelia J, Bolaños, Carlos A, Kabbaj, Mohamed, Xiao, Guanghua, Neve, Rachael L, Hurd, Yasmin L, Oosting, Ronald S, Fan, Gouping, Morrison, John H, and Nestler, Eric J

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Behavioral and Social Science, Brain Disorders, Neurosciences, Basic Behavioral and Social Science, Drug Abuse (NIDA only), Mental Health, Substance Misuse, Good Health and Well Being, Animals, Chronic Disease, Cocaine, DNA (Cytosine-5-)-Methyltransferases, DNA Methylation, DNA Methyltransferase 3A, Dendritic Spines, Depression, Dominance-Subordination, Dopamine Uptake Inhibitors, Emotions, Gene Expression Regulation, Male, Mice, Mice, Inbred C57BL, Neuronal Plasticity, Neurons, Nucleus Accumbens, Rats, Rats, Long-Evans, Rats, Sprague-Dawley, Stress, Psychological, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract

Despite abundant expression of DNA methyltransferases (Dnmts) in brain, the regulation and behavioral role of DNA methylation remain poorly understood. We found that Dnmt3a expression was regulated in mouse nucleus accumbens (NAc) by chronic cocaine use and chronic social defeat stress. Moreover, NAc-specific manipulations that block DNA methylation potentiated cocaine reward and exerted antidepressant-like effects, whereas NAc-specific Dnmt3a overexpression attenuated cocaine reward and was pro-depressant. On a cellular level, we found that chronic cocaine use selectively increased thin dendritic spines on NAc neurons and that DNA methylation was both necessary and sufficient to mediate these effects. These data establish the importance of Dnmt3a in the NAc in regulating cellular and behavioral plasticity to emotional stimuli.

Published
2010

36. Essential Role for RGS9 in Opiate Action

Author

Zachariou, Venetia, Georgescu, Dan, Sanchez, Nick, Rahman, Zia, DiLeone, Ralph, Berton, Olivier, Neve, Rachael L., Sim-Selley, Laura J., Selley, Dana E., Gold, Stephen J., and Nestler, Eric J.

Published
2003

38. Cocaine-Induced Chromatin Modifications Associate With Increased Expression and Three-Dimensional Looping of Auts2

Author

Engmann, Olivia, Labonté, Benoit, Mitchell, Amanda, Bashtrykov, Pavel, Calipari, Erin S., Rosenbluh, Chaggai, Loh, Yong-Hwee E., Walker, Deena M., Burek, Dominika, Hamilton, Peter J., Issler, Orna, Neve, Rachael L., Turecki, Gustavo, Hurd, Yasmin, Chess, Andrew, Shen, Li, Mansuy, Isabelle, Jeltsch, Albert, Akbarian, Schahram, and Nestler, Eric J.

Published
2017
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43. Regulation of Cocaine Reward by CREB

Author

Carlezon, William A., Thome, Johannes, Olson, Valerie G., Lane-Ladd, Sarah B., Brodkin, Edward S., Hiroi, Noboru, Duman, Ronald S., Neve, Rachael L., and Nestler, Eric J.

Published
1998

45. The Anti-Amyloid Monoclonal Antibody Lecanemab: 16 Cautionary Notes

Author

Kepp, Kasper P., primary, Sensi, Stefano L., additional, Johnsen, Kasper B., additional, Barrio, Jorge R., additional, Høilund-Carlsen, Poul F., additional, Neve, Rachael L., additional, Alavi, Abass, additional, Herrup, Karl, additional, Perry, George, additional, Robakis, Nikolaos K., additional, Vissel, Bryce, additional, and Espay, Alberto J., additional

Published
2023
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49. Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility

Author

Bagot, Rosemary C., Cates, Hannah M., Purushothaman, Immanuel, Lorsch, Zachary S., Walker, Deena M., Wang, Junshi, Huang, Xiaojie, Schlüter, Oliver M., Maze, Ian, Peña, Catherine J., Heller, Elizabeth A., Issler, Orna, Wang, Minghui, Song, Won-min, Stein, Jason. L., Liu, Xiaochuan, Doyle, Marie A., Scobie, Kimberly N., Sun, Hao Sheng, Neve, Rachael L., Geschwind, Daniel, Dong, Yan, Shen, Li, Zhang, Bin, and Nestler, Eric J.

Published
2016
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50. Histone arginine methylation in cocaine action in the nucleus accumbens

Author

Damez-Werno, Diane M., Sun, HaoSheng, Scobie, Kimberly N., Shao, Ningyi, Rabkin, Jaclyn, Dias, Caroline, Calipari, Erin S., Maze, Ian, Pena, Catherine J., Walker, Deena M., Cahill, Michael E., Chandra, Ramesh, Gancarz, Amy, Mouzon, Ezekiell, Landry, Joseph A., Cates, Hannah, Lobo, Mary-Kay, Dietz, David, Allis, C. David, Guccione, Ernesto, Turecki, Gustavo, Defilippi, Paola, Neve, Rachael L., Hurd, Yasmin L., Shen, Li, and Nestler, Eric J.

Published
2016

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