Insulin resistance in brain alters dopamine turnover and causes behavioral disorders
Abstract
Both types 1 and 2 diabetes are associated with increased risks of age-related decay in cognitive function and mood disorders, especially depression. Insulin action has been shown to regulate neuronal signaling and plasticity. Here we investigate whether brain-specific knockout of insulin receptor (NIRKO) in mice causes behavioral changes and how these are mechanistically linked. We find that NIRKO mice exhibit age-related anxiety and depressive-like behavior. This is due to altered mitochondrial function, aberrant monoamine oxidase (MAO) expression, and increased dopamine turnover in the mesolimbic system, and can be reversed by treatment with Mao inhibitors. Thus, brain insulin resistance alters dopamine turnover and induces anxiety and depressive-like behaviors. These findings demonstrate a potential molecular link between central insulin resistance and behavioral disorders.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- March 2015
- DOI:
- 10.1073/pnas.1500877112
- Bibcode:
- 2015PNAS..112.3463K