Changes in intracellular calcium ((Ca2+)cyt) metabolism have been found in aged and Alzheimer's disease (AD) neurons and fibroblasts and it has been suggested that altered (Ca2+)cyt plays a role in the loss of neuronal function and eventual neuron death in aging and AD. In my previous work I have shown that there is accelerated neuron death and abnormally regulated (Ca2+)cyt in the trisomy 16 (Ts16) mouse. The goal of this pilot project is to systematically compare the Ca2+ defect in Ts16 with the reported changes in Ca2+ metabolism in aging and AD to determine whether Ts16 can model these Ca2+ defect(s). This study will employ Ca2+ imaging, biochemical assays of ATP production, measurements of neuron survival and confocal microscopy (for measurements of reactive oxygen species and mitochondrial function) to determine whether the Ts16 system does model some of the reported age- and AD-related changes in Ca2+ homeostasis. Pharmacological interventions which correct the Ts16Ca2+ defect will be tested to address the question of whether correcting a (Ca2+)cyt defect will improve neuron function and survival. If these pilot experiments are successful, future work will be directed towards determining the molecular mechanisms underlying the Ts16Ca2+ defect. These experiments will lead to an improved understanding of normal Ca2+ homeostasis. A long term goal of this work will be to determine how triplication of mouse chromosome 16 produces this abnormal regulation of Ca2+ and the extent to which the pertinent gene(s) and their products are affected in human pathology.
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| Haydar, T F; Bambrick, L L; Krueger, B K et al. (1999) Organotypic slice cultures for analysis of proliferation, cell death, and migration in the embryonic neocortex. Brain Res Brain Res Protoc 4:425-37 |
| Cheng, A; Krueger, B K; Bambrick, L L (1999) MAP5 expression in proliferating neuroblasts. Brain Res Dev Brain Res 113:107-13 |
| Bambrick, L L; Krueger, B K (1999) Neuronal apoptosis in mouse trisomy 16: mediation by caspases. J Neurochem 72:1769-72 |
