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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lacefield, Clay O. Arguello, P. Alexander Lepagnol-bestel, Aude-marie Blazeski, Richard Xiao, Lan Kvajo, Mirna Mckellar, Heather O'donnell, James M. Levy, Rebecca J. Mason, Carol A. Karayiorgou, Maria Simonneau, Michel Drew, Liam J. Macdermott, Amy B. Gogos, Joseph A. |
| Description | Author Affiliation: Kvajo M ( Department of Psychiatry, Columbia University Medical Center, New York, NY 10032, USA.); |
| Abstract | Carefully designed animal models of genetic risk factors are likely to aid our understanding of the pathogenesis of schizophrenia. Here, we study a mouse strain with a truncating lesion in the endogenous Disc1 ortholog designed to model the effects of a schizophrenia-predisposing mutation and offer a detailed account of the consequences that this mutation has on the development and function of a hippocampal circuit. We uncover widespread and cumulative cytoarchitectural alterations in the dentate gyrus during neonatal and adult neurogenesis, which include errors in axonal targeting and are accompanied by changes in short-term plasticity at the mossy fiber/CA3 circuit. We also provide evidence that cAMP levels are elevated as a result of the Disc1 mutation, leading to altered axonal targeting and dendritic growth. The identified structural alterations are, for the most part, not consistent with the growth-promoting and premature maturation effects inferred from previous RNAi-based Disc1 knockdown. Our results provide support to the notion that modest disturbances of neuronal connectivity and accompanying deficits in short-term synaptic dynamics is a general feature of schizophrenia-predisposing mutations. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 49 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Axons Metabolism Hippocampus Nerve Tissue Proteins Neuronal Plasticity Action Potentials Animals Animals, Newborn Cell Proliferation Cells, Cultured Cyclic AMP Cyclic Nucleotide Phosphodiesterases, Type 4 Dendrites Physiology Dentate Gyrus Cytology Growth & Development Immunohistochemistry Long-Term Potentiation Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Mossy Fibers, Hippocampal Genetics Neurogenesis Neurons Patch-Clamp Techniques Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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