BMI Progress Reports 2020 // Prof. Sanid's Lab: Elias Gebara - Mitofusin-2 in the nucleus accumbens links high anxiety with mitochondrial and neuronal structure and function and behavior

Mitochondrial dysfunction is increasingly implicated in brain function and psychopathologies. Mitofusin 2 (Mfn2) is molecule involved in mitochondrial dynamics and is essential for the regulation of energy production under stress conditions and for mitigating mitochondrial resulting from environmental challenges. In this study, we investigate the involvement of Mfn2 in a brain region, the nucleus accumbens that plays a key role in motivation and is implicated in depression, in the vulnerability to develop anxiety and depression following stress exposure. Wistar outbred rats were first classified as high- or low-anxious based on natural variation for anxiety-like behavior on the elevated plus maze. High-Anxious rat displayed a decrease in Mfn2 RNA and protein levels, coupled with a change mitochondria morphology and function. These changes results in an alteration in neuronal morphology and physiology affecting the behavior. We injected a Mfn2 overexpressing AAV in the nucleus accumbens of high-Anxious rat and we found that after 4 weeks of incubation we restore the neuronal morphology and the behavior. Our results suggests that mfn2 plays a major role in the neuronal function and the anxiety related behavior.