7 results on '"Olde Loohuis N"'
Search Results
2. Chromosome 1p21.3 microdeletions comprising DPYD and MIR137 are associated with intellectual disability
- Author
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Willemsen, M.H., Valles, A., Kirkels, L.A.M.H., Mastebroek, M., Olde Loohuis, N., Kos, A., Wissink, W.M., Brouwer, A.P.M. de, Nillesen, W.M., Pfundt, R., Holder-Espinasse, M., Vallee, L., Andrieux, J., Coppens-Hofman, M.C., Rensen, H., Hamel, B.C.J., Bokhoven, H. van, Aschrafi, A., Kleefstra, T., Willemsen, M.H., Valles, A., Kirkels, L.A.M.H., Mastebroek, M., Olde Loohuis, N., Kos, A., Wissink, W.M., Brouwer, A.P.M. de, Nillesen, W.M., Pfundt, R., Holder-Espinasse, M., Vallee, L., Andrieux, J., Coppens-Hofman, M.C., Rensen, H., Hamel, B.C.J., Bokhoven, H. van, Aschrafi, A., and Kleefstra, T.
- Abstract
Contains fulltext : 96723.pdf (publisher's version ) (Closed access), Background MicroRNAs (miRNAs) are non-coding gene transcripts involved in post-transcriptional regulation of genes. Recent studies identified miRNAs as important regulators of learning and memory in model organisms. So far, no mutations in specific miRNA genes have been associated with impaired cognitive functions. Methods and results In three sibs and two unrelated patients with intellectual disability (ID), overlapping 1p21.3 deletions were detected by genome-wide array analysis. The shortest region of overlap included dihydropyrimidine dehydrogenase (DPYD) and microRNA 137 (MIR137). DPYD is involved in autosomal recessive dihydropyrimidine dehydrogenase deficiency. Hemizygous DPYD deletions were previously suggested to contribute to a phenotype with autism spectrum disorder and speech delay. Interestingly, the mature microRNA transcript microRNA-137 (miR-137) was recently shown to be involved in modulating neurogenesis in adult murine neuronal stem cells. Therefore, this study investigated the possible involvement of MIR137 in the 1p21.3-deletion phenotype. The patients displayed a significantly decreased expression of both precursor and mature miR-137 levels, as well as significantly increased expression of the validated downstream targets microphthalmia-associated transcription factor (MITF) and Enhancer of Zeste, Drosophila, Homologue 2 (EZH2), and the newly identified target Kruppel-like factor 4 (KLF4). The study also demonstrated significant enrichment of miR-137 at the synapses of cortical and hippocampal neurons, suggesting a role of miR-137 in regulating local synaptic protein synthesis machinery. Conclusions This study showed that dosage effects of MIR137 are associated with 1p21.3 microdeletions and may therefore contribute to the ID phenotype in patients with deletions harbouring this miRNA. A local effect at the synapse might be responsible.
- Published
- 2011
3. Acute pain increases phosphorylation of DCLK-long in the Edinger-Westphal nucleus but not in the hypothalamic paraventricular nucleus of the rat.
- Author
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Rouwette, T.P.H., Kozicz, L.T., Olde Loohuis, N., Gaszner, B., Vreugdenhil, E., Scheffer, G.J., Roubos, E.W., Vissers, K.C.P., Scheenen, W.J.J.M., Rouwette, T.P.H., Kozicz, L.T., Olde Loohuis, N., Gaszner, B., Vreugdenhil, E., Scheffer, G.J., Roubos, E.W., Vissers, K.C.P., and Scheenen, W.J.J.M.
- Abstract
1 oktober 2010, Contains fulltext : 87902.pdf (publisher's version ) (Closed access), The doublecortin-like kinase (DCLK) gene is crucially involved in neuronal plasticity and microtubule-guided retrograde transport of signaling molecules. We have explored the possibility that DCLK is involved in pain-induced signaling events in adult male Wistar rats. Our results show that both DCLK-short and DCLK-long splice variants are present in the cell body and proximal dendrites of neurons in stress-related nuclei, ie, the paraventricular nucleus of the hypothalamus (PVN) and the non-preganglionic Edinger-Westphal nucleus (npEW) in the rostroventral periaqueductal grey. We found that DCLK-long but not DCLK-short is phosphorylated in its serine/proline-rich domain. Furthermore, we demonstrate that phosphorylation of DCLK-long in the npEW is increased by acute pain, whereas DCLK-long phosphorylation in the PVN remains unaffected. This is the first report revealing that DCLK isoforms in the PVN and npEW occur in the adult mammalian brain and that pain differentially affects DCLK-long-mediated neuronal plasticity in these 2 stress-sensitive brain centers. PERSPECTIVE: Pain is a burden for society and the individual, and although the mechanisms underlying pain are relatively well known, its treatment remains difficult and incomplete. Pain stress can lead to diseases like chronic pain and depression. The differential DCLK-phosphorylation in stress-sensitive brain areas is a potential novel therapeutic target in pain research.
- Published
- 2010
4. Chromosome 1p21.3 microdeletions comprising DPYD and MIR137 are associated with intellectual disability
- Author
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Willemsen, M. H., primary, Valles, A., additional, Kirkels, L. A. M. H., additional, Mastebroek, M., additional, Olde Loohuis, N., additional, Kos, A., additional, Wissink-Lindhout, W. M., additional, de Brouwer, A. P. M., additional, Nillesen, W. M., additional, Pfundt, R., additional, Holder-Espinasse, M., additional, Vallee, L., additional, Andrieux, J., additional, Coppens-Hofman, M. C., additional, Rensen, H., additional, Hamel, B. C. J., additional, van Bokhoven, H., additional, Aschrafi, A., additional, and Kleefstra, T., additional
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- 2011
- Full Text
- View/download PDF
5. MicroRNA networks direct neuronal development and plasticity
- Author
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Olde Loohuis, N. F. M., primary, Kos, A., additional, Martens, G. J. M., additional, Van Bokhoven, H., additional, Nadif Kasri, N., additional, and Aschrafi, A., additional
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- 2011
- Full Text
- View/download PDF
6. MicroRNA-181 promotes synaptogenesis and attenuates axonal outgrowth in cortical neurons.
- Author
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Kos A, Olde Loohuis N, Meinhardt J, van Bokhoven H, Kaplan BB, Martens GJ, and Aschrafi A
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- Animals, Antagomirs metabolism, Apoptosis, Cells, Cultured, Cerebral Cortex cytology, Embryo, Mammalian cytology, Female, Gene Regulatory Networks, Genetic Vectors genetics, Genetic Vectors metabolism, HEK293 Cells, Humans, MicroRNAs antagonists & inhibitors, MicroRNAs genetics, Neurogenesis, RNA chemistry, RNA isolation & purification, RNA metabolism, Rats, Rats, Wistar, Sequence Analysis, RNA, Signal Transduction, Axons metabolism, Cerebral Cortex metabolism, MicroRNAs metabolism
- Abstract
MicroRNAs (miRs) are non-coding gene transcripts abundantly expressed in both the developing and adult mammalian brain. They act as important modulators of complex gene regulatory networks during neuronal development and plasticity. miR-181c is highly abundant in cerebellar cortex and its expression is increased in autism patients as well as in an animal model of autism. To systematically identify putative targets of miR-181c, we repressed this miR in growing cortical neurons and found over 70 differentially expressed target genes using transcriptome profiling. Pathway analysis showed that the miR-181c-modulated genes converge on signaling cascades relevant to neurite and synapse developmental processes. To experimentally examine the significance of these data, we inhibited miR-181c during rat cortical neuronal maturation in vitro; this loss-of miR-181c function resulted in enhanced neurite sprouting and reduced synaptogenesis. Collectively, our findings suggest that miR-181c is a modulator of gene networks associated with cortical neuronal maturation.
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- 2016
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7. Elevated microRNA-181c and microRNA-30d levels in the enlarged amygdala of the valproic acid rat model of autism.
- Author
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Olde Loohuis NF, Kole K, Glennon JC, Karel P, Van der Borg G, Van Gemert Y, Van den Bosch D, Meinhardt J, Kos A, Shahabipour F, Tiesinga P, van Bokhoven H, Martens GJ, Kaplan BB, Homberg JR, and Aschrafi A
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- Amygdala pathology, Animals, Autistic Disorder chemically induced, Autistic Disorder pathology, Disease Models, Animal, Neurons metabolism, Neurons pathology, Rats, Social Behavior, Transcriptome, Valproic Acid, Amygdala metabolism, Autistic Disorder genetics, Autistic Disorder metabolism, MicroRNAs metabolism
- Abstract
Autism spectrum disorders are severe neurodevelopmental disorders, marked by impairments in reciprocal social interaction, delays in early language and communication, and the presence of restrictive, repetitive and stereotyped behaviors. Accumulating evidence suggests that dysfunction of the amygdala may be partially responsible for the impairment of social behavior that is a hallmark feature of ASD. Our studies suggest that a valproic acid (VPA) rat model of ASD exhibits an enlargement of the amygdala as compared to controls rats, similar to that observed in adolescent ASD individuals. Since recent research suggests that altered neuronal development and morphology, as seen in ASD, may result from a common post-transcriptional process that is under tight regulation by microRNAs (miRs), we examined genome-wide transcriptomics expression in the amygdala of rats prenatally exposed to VPA, and detected elevated miR-181c and miR-30d expression levels as well as dysregulated expression of their cognate mRNA targets encoding proteins involved in neuronal system development. Furthermore, selective suppression of miR-181c function attenuates neurite outgrowth and branching, and results in reduced synaptic density in primary amygdalar neurons in vitro. Collectively, these results implicate the small non-coding miR-181c in neuronal morphology, and provide a framework of understanding how dysregulation of a neurodevelopmentally relevant miR in the amygdala may contribute to the pathophysiology of ASD., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
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