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| Item Type: | Article |
|---|---|
| Title: | Metformin reverses early cortical network dysfunction and behavior changes in Huntington's disease |
| Creators Name: | Arnoux, I., Willam, M., Griesche, N., Krummeich, J., Watari, H., Offermann, N., Weber, S., Narayan Dey, P., Chen, C., Monteiro, O., Buettner, S., Meyer, K., Bano, D., Radyushkin, K., Langston, R., Lambert, J.J., Wanker, E., Methner, A., Krauss, S., Schweiger, S. and Stroh, A. |
| Abstract: | Catching primal functional changes in early, 'very far from disease onset' (VFDO) stages of Huntington's disease is likely to be the key to a successful therapy. Focusing on VFDO stages, we assessed neuronal microcircuits in premanifest Hdh150 knock-in mice. Employing in vivo two-photon Ca(2+) imaging, we revealed an early pattern of circuit dysregulation in the visual cortex- one of the first regions affected in premanifest Huntington's disease - characterized by an increase in activity, an enhanced synchronicity and hyperactive neurons. These findings are accompanied by aberrations in animal behavior. We furthermore show that the anti-diabetic drug metformin diminishes aberrant Huntingtin protein load and fully restores both, early network activity patterns and behavioral aberrations. This network-centered approach reveals a critical window of vulnerability far before clinical manifestation and establishes metformin as a promising candidate for a chronic therapy starting early in premanifest Huntington's disease pathogenesis long before the onset of clinical symptoms. |
| Keywords: | Huntington Disease, In Vivo Calcium Imaging, Cortical Microcircuits, Neuronal Hyperactivity, Metformin, Animals, Caenorhabditis elegans |
| Source: | eLife |
| ISSN: | 2050-084X |
| Publisher: | eLife Sciences Publications |
| Volume: | 7 |
| Page Range: | e38744 |
| Date: | 4 September 2018 |
| Official Publication: | https://doi.org/10.7554/eLife.38744 |
| PubMed: | View item in PubMed |
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