3. Huntington\'s Disease (HD) is a rare and fatal neurodegenerative n\'s Disease

Question

3. Huntington's Disease (HD) is a rare and fatal neurodegenerative n's Disease (HD) is a rare and fatal neurodegenerative disorder that results in hyperkinesia. One of the issues that occurs as a result of Huntington's is deficits in axonal transport. For example. mutations in the huntingtin (Htt) gene result in the loss of anterograde transport of organeles sach as mitochondria. Among their many functions, mitochondria are thought to sequester Cat ions. You working with an animal model of HD. You are recording the responses of neurons receiving synaptic inputs from cells in normal tissue and HD tissue. You note that these responses occur 3-5x more often in the HD tissue than that of normal tissue. Propose a mechanism wherein the Hitt mutation could produce this increase in the responses of the HD neurons Page 2 c

Explanation / Answer

In case of Huntington disease is a progressive, fatal neurodegenarative disorder caused by an expansion of CAG ( genetic code for glutamine) repeats in the coding region of the Huntington gene. This results in the medium-sized spiny (MSNs) and cortical pyramidal neurons. Degenerated neurons causes a loss of input to the GPe which would induce an imbalance in the basal ganglia circuitry, leading to inhibition of the subthalamic nucleus, which in turn would release inhibition to the thalamus, inducing overflow of glutamate activity in the cortex and hyperkinetic movements. Thus, increased level of glutamate (major neurotransmitter) causes increase in responses of the HD neurons.

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