Event Title

Death of Subthalamic Nucleus Neurons due to Mitochondrial Oxidative Stress in Huntington’s Disease Mouse Models

Session Number

Q35

Advisor(s)

Mark Bevan, Northwestern University

Location

B-133

Start Date

28-4-2016 12:45 PM

End Date

28-4-2016 1:10 PM

Disciplines

Neuroscience and Neurobiology

Abstract

Huntington’s Disease (HD) is a neurodegenerative disease that belongs to a class of hyperkinetic disorders which affect the basal ganglia. The role of the subthalamic nucleus (STN) in HD progression is relatively uncharacterized although prior experiments have shown that STN neuron firing is disrupted during HD. In other brain areas, mitochondrial oxidative stress has been shown to have a role in neuronal dysfunction in HD. This oxidative stress can also lead to production of hydrogen peroxide which is known to disrupt firing. Thus, to elucidate the role of oxidative stress in STN dysfunction, we used electrophysiological recordings to test the effect of degrading hydrogen peroxide with catalase on the firing phenotype of neurons. Catalase was able to return firing to normal providing evidence that mitochondrial oxidative stress underlies slowed firing. We also looked at potential cell loss due to mitochondrial oxidative stress by studying differences in the number of STN neurons in wild- type and 12 month old Q175 mice using unbiased stereological counting techniques. Our results showed that Q175 mice had a significantly lower number of STN neurons than wild type littermates. Thus STN neurons are dysfunctional in HD models due to mitochondrial oxidative stress, ultimately causing cell loss.


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Apr 28th, 12:45 PM Apr 28th, 1:10 PM

Death of Subthalamic Nucleus Neurons due to Mitochondrial Oxidative Stress in Huntington’s Disease Mouse Models

B-133

Huntington’s Disease (HD) is a neurodegenerative disease that belongs to a class of hyperkinetic disorders which affect the basal ganglia. The role of the subthalamic nucleus (STN) in HD progression is relatively uncharacterized although prior experiments have shown that STN neuron firing is disrupted during HD. In other brain areas, mitochondrial oxidative stress has been shown to have a role in neuronal dysfunction in HD. This oxidative stress can also lead to production of hydrogen peroxide which is known to disrupt firing. Thus, to elucidate the role of oxidative stress in STN dysfunction, we used electrophysiological recordings to test the effect of degrading hydrogen peroxide with catalase on the firing phenotype of neurons. Catalase was able to return firing to normal providing evidence that mitochondrial oxidative stress underlies slowed firing. We also looked at potential cell loss due to mitochondrial oxidative stress by studying differences in the number of STN neurons in wild- type and 12 month old Q175 mice using unbiased stereological counting techniques. Our results showed that Q175 mice had a significantly lower number of STN neurons than wild type littermates. Thus STN neurons are dysfunctional in HD models due to mitochondrial oxidative stress, ultimately causing cell loss.