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Abstract

Neurogenesis in age-matched calcium ion channel mutant mice, leaner and tottering

Texas A&M University College of Veterinary Medicine and Biomendical Sciences,

Department of Veterinary Anatomy and Public Health, College Station, TX 77843

Chang A.*, Wyse R., Gomez F., and Abbott LC

Neurogenesis in the adult brain has been shown to definitively occur in only two specific areas: the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. The hippocampus, as part of the limbic system, plays a significant role in memory formation, spatial learning and behavior. Homozygous leaner and tottering mice carry a mutation in the pore-forming subunit of neuronal P/Q-type calcium ion channels, which leads to an imbalance in calcium homeostasis. Calcium is important because it is a known signaling molecule in synaptic transmission, cell growth and survivability. Because P/Q type calcium channels are highly expressed in the hippocampus, we expect to see mice with this mutation to show a correlational change in neuronal cell growth and survivability. We are investigating neural proliferation differences in the hippocampus of 6 month aged calcium mutant mice compared to age-matched wild type mice. Mice were given seven doses over three days of bromodeoxyuridine (BrdU; 100 mg/Kg), a known marker for dividing cells. Mice were anesthetized, perfused with 4% phosphate-buffered paraformaldehyde the brain was cryoprotected and rapidly frozen for frozen histological sectioning. Immunohistochemistry was performed on 15 micron coronal sections. Previously, age-matched leaner mice (postnatal) (P) 45 and P100 have been examined. At P45 leaner and tottering mice have altered cell proliferation in the hippocampus actually exhibiting cell proliferation rates higher than wild type mice, which levels off by P100. At P100 leaner and tottering show a significant decrease in proliferation than wild type mice. We are investigating further whether the proliferation rate remains significantly lower in mutant mice compared to wild type mice as they age.