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Updated: May 31, 2026
08:27
Single Synapse Indicators of Glutamate Release and Uptake in Acute Brain Slices from Normal and Huntington Mice
Published on: March 11, 2020
Striatal Neuron Excitability Is Regulated by Huntingtin in the Adult Brain
Jessica C Barron1, Meghan L Greenland1, Samantha J Carew1
1Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's, Newfoundland A1B 3V6, Canada.
Eneuro
|May 28, 2026
Summary
Deleting wild-type huntingtin (wtHTT) in adult mice impaired neuronal excitability and caused neuroinflammation. This suggests caution is needed with non-selective HTT-lowering therapies for Huntington
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder.
- It stems from a mutation in the huntingtin (HTT) gene, leading to neuronal dysfunction and brain atrophy.
- Wild-type HTT (wtHTT) loss-of-function is an understudied aspect of HD pathophysiology.
Purpose of the Study:
- To investigate the effects of wtHTT deletion in the adult mouse brain.
- To understand the consequences of wtHTT loss in regions vulnerable to HD, like the striatum and cortex.
Main Methods:
- Conditional inactivation of wtHTT in adult male and female Httfl/fl mice.
- Assessment of neuronal excitability, neuroinflammation, tissue organization, spine morphology, and motor behavior.
Main Results:
- wtHTT loss decreased intrinsic neuronal excitability in striatal SPNs.
- A significant neuroinflammatory response was observed.
- Tissue organization, spine morphology, and motor behavior were unaffected.
Conclusions:
- wtHTT is crucial for maintaining neuronal health in the adult brain.
- Non-selective HTT-lowering therapies for HD may have adverse consequences due to wtHTT reduction.
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