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Published on: January 11, 2013
Metformin reverses early cortical network dysfunction and behavior changes in Huntington's disease.
Isabelle Arnoux1, Michael Willam2, Nadine Griesche3
1Institute of Pathophysiology, Focus Program Translational Neurosciences, University Medical Center, Mainz, Germany.
Elife
|September 5, 2018
Summary
Early Huntington's disease (HD) stages show abnormal brain activity and behavior in mice. The drug metformin reversed these changes, offering hope for early HD therapy.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Huntington's disease (HD) is a neurodegenerative disorder.
- Early detection of functional changes before symptom onset is crucial for therapy.
- Preclinical models are essential for understanding early disease mechanisms.
Purpose of the Study:
- To identify early functional changes in neuronal circuits in premanifest Huntington's disease.
- To investigate the therapeutic potential of metformin in early-stage Huntington's disease.
Main Methods:
- Utilized Hdh150 knock-in mice, a model for Huntington's disease.
- Employed in vivo two-photon Ca2+ imaging to assess neuronal activity in the visual cortex.
- Conducted behavioral tests to evaluate functional deficits.
Main Results:
- Observed increased neuronal activity, enhanced synchronicity, and hyperactive neurons in the visual cortex of premanifest mice.
- Documented accompanying behavioral aberrations.
- Demonstrated that metformin reduces Huntingtin protein, restores network activity, and corrects behavioral deficits.
Conclusions:
- Early circuit dysregulation occurs in premanifest Huntington's disease, preceding clinical symptoms.
- Metformin shows promise as a therapeutic agent for early intervention in Huntington's disease.
- A network-centered approach identifies a critical therapeutic window in early pathogenesis.
Keywords:
C. elegansHuntington diseasecortical microcircuitsin vivo calcium imagingmetforminmouseneuronal hyperactivityneuroscienceMore Related Videos
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