Mechanisms that Cause Synaptic Dystrophy in Alzheimer's Disease
Alzheimer's disease is caused by the build-up of the β-amyloid protein (A&beta) in the brain. Recent studies suggest that toxic oligomeric species of A&beta damage the normal communication between nerve cells by causing the degeneration of nerve synapses. This toxic effect results in the formation of dystrophic neurites, which are degenerating nerve terminals. Work in the laboratory has demonstrated a possible mechanism for this toxic effect. Our studies have shown that neurotoxicity may be caused by an increase in the level of cytoplasmic calcium, due to the activation of voltage-gated calcium channels. The project examines this hypothesis and tests the idea that calcium dysfunction underlies the formation of dystrophic neurites.
The project involves the following sets of experiments/approaches:
- Primary cultures of rat hippocampal neurons isolated and grown in culture
- The effect of A&beta protein on cytoplasmic calcium levels assessed using calcium fluorescence indicator method
- The effect of receptor and ion channel blockers to inhibit the effect of A&beta on calcium is being assessedd)
- The effect of A&beta on neuronal morphology (neurite outgrowth and dendritic spine density) is being assessed