Neural cell proliferation and survival in the hippocampus of adult CaV 2.1 calcium ion channel mutant mice
| Autor: | Fikru Nigussie, Eid A. Moussa, Bhupinder Bawa, Pei-San Huang, Kris Lukauskis, Louise C. Abbott |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Cell Survival Spatial Learning Hippocampus Hippocampal formation Biology Sholl analysis Mice Mice Neurologic Mutants 03 medical and health sciences Calcium Channels N-Type 0302 clinical medicine Animals Molecular Biology Cell Proliferation Neurons Glial fibrillary acidic protein Cell growth General Neuroscience Dentate gyrus Calcium channel Neurogenesis Molecular biology Mice Inbred C57BL 030104 developmental biology Bromodeoxyuridine Immunology biology.protein Calcium Neurology (clinical) 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Brain Research. 1650:162-171 |
| ISSN: | 0006-8993 |
| Popis: | Tottering mutant mice carry a mutation in the pore-forming subunit (α1A) of CaV2.1 (P/Q-type) voltage-gated calcium ion (Ca2+) channels resulting in reduced neuronal Ca2+ current density. We assessed male tottering mice for spatial learning using the Morris water maze. Tottering mice performed worse than wild type mice, suggesting abnormal hippocampal function. Because Ca2+ influx via voltage-dependent Ca2+ channels regulates neuronal survival and function, we assessed hippocampus volume and cell density using hematoxylin and eosin stained serial sections. Adult hippocampal neurogenesis was assessed using 5-bromo-2'-deoxyuridine (BrdU) labeling with fluorescent immunohistochemistry (IHC) and proliferating cell nuclear antigen (PCNA) with diaminobenzidine IHC. We double-labeled neurons using fluorescence IHC with BrdU-neuronal nuclei (Neu-N) or double labeling of astrocytes using BrdU-glial fibrillary protein, respectively, to assess cell proliferation and survival. We assessed numbers of dying cells using fluoro-Jade histochemistry. Decreased hippocampal volume, increased dentate hilar and hippocampal CA1 cell densities were observed in tottering mice compared to wild type mice. Cell proliferation was increased in the hilus and CA2 region of tottering mice compared to wild type mice. Dendritic intersections in Sholl analysis were decreased for tottering mouse CA1 pyramidal neurons compared to wild type mice. The increased regional cell density coincides with increases in cell proliferation in similar, non-neurogenic areas of the hippocampus of tottering mice. Thus, hippocampal alterations observed in adult tottering mice appear to result from changes in neuronal morphology and proliferation in non-neurogenic areas of the hippocampus, and less through altered adult hippocampal neurogenesis or cell death. |
| Databáze: | OpenAIRE |
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