Abstract

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Our overarching hypothesis is that the behavioral reprogramming induced by peripubertal stress is mediated by decreased signaling of the adipokine eNampt and subsequent impairment of the NAD+/SIRT1 pathway in the NAc. Therefore, our specific hypothesis 1 is that Sirt1 overexpression in the nucleus accumbens (NAc) or normalization of plasmatic levels of eNampt would revert the stressinduced behavioral alterations. Our specific hypothesis 2 is that a nutritional intervention with the NAD+-boosting compound NMN would prevent the alterations in brain and behavior exhibited by stressed mice. We will test our hypotheses through two main objectives :

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Objective 1
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To evaluate whether decreased eNampt levels and impaired SIRT1 signaling in the NAc underlie the behavioral alterations exhibited by peripubertal stressed mice

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Objective 2

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To test the therapeutic potential of the NAD+-boosting compound NMN to counteract the negative impact of early life-stress on brain function and behavior

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