title: Neural cell proliferation and survival in the hippocampus of adult CaV 2.1 calcium ion channel mutant mice.
abstract: 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.
authors: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, 105 Magruder Hall, Corvallis, OR 97331, USA.
authors: Fikru
authors: F
authors: Nigussie
authors: 700 Stewart Ave., Apt. 43, Ithaca, NY 14850, USA.
authors: Pei-San
authors: PS
authors: Huang
authors: Department of Anesthesiology, University of California, San Diego Health System, 200 West Arbor Drive, San Diego, CA 92103, USA.
authors: Kris
authors: K
authors: Lukauskis
authors: Department of Diagnostic Medicine/Pathology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66502, USA.
authors: Bhupinder
authors: B
authors: Bawa
authors: Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt.
authors: Eid
authors: E
authors: Moussa
authors: Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, 4458 TAMU, College Station, TX 77843-4458, USA. Electronic address: labbott@cvm.tamu.edu.
authors: Louise C
authors: LC
authors: Abbott
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine; D002118:Calcium / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000235:genetics* / Q000378:metabolism*; D049109:Cell Proliferation; D002470:Cell Survival; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009474:Neurons / Q000378:metabolism; D065853:Spatial Learning
chemical_list: D001973:Bromodeoxyuridine; D002118:Calcium; D020864:Calcium Channels, N-Type
keywords: Adult hippocampal neurogenesis; CaV 2.1 voltage-gated calcium ion channels; Dentate gyrus; P/Q calcium ion channels; PCNA; Tottering mouse