I will be looking at the effects of Huntington's Disease on NMDA receptors and their subunits. 1. Determine levels of expression of each subunit and the subunit composition of NMDA receptors in rat striatum of control and transgenic mice expressing mutant huntingtin. Hypothesis: The expression levels and subunit composition of NMDA receptors will be altered in mutant mice compared to controls due to selective neurodegeneration or compensatory mechanisms. 2. Examine the mechanism(s) by which NR1/NR2B type NMDA receptors show an increased current density when expressed in HEK cells along with mutant huntingtin (htt138). Hypothesis: An increase in response of NR1/NR2B receptors occurs in HEK cells transfected with mutant huntingtin (htt138). 3. Determine levels of expression of each subunit and the subunit composition of NMDA receptors in normal rat striatum as compared to the subunit composition in other regions of normal mouse brain. Hypothesis: The striatum expresses more NR1/NR2B receptors than other regions making the neurons especially susceptible to excitotoxicity when mutant huntingtin is present. 4. Use immunohistochemistry to determine levels of expression of each subunit of NMDA receptors in rat basal ganglia structures, including the striatum, of control and transgenic mice expressing mutant huntingtin. Hypothesis: The levels of expression of subunits will be selectively affected based on the cell types within the striatum and throughout the BG.
| Jarabek, Bryan R; Yasuda, Robert P; Wolfe, Barry B (2004) Regulation of proteins affecting NMDA receptor-induced excitotoxicity in a Huntington's mouse model. Brain 127:505-16 |
