Maternal high fat diet programs stress-induced behavioral disorder in adult offspring

- The effects of maternal HFD on offspring behavior did not persist into adulthood.
- Maternal HFD sensitizes offspring to the detrimental effects of stress on behavior.
- CUMS-treated offspring of HFD-fed dams have increased CGRP levels in hippocampus.
- Central infusion of CGRP antagonist produced antidepressant effect in HFD + CUMS rats.
- Maternal HFD attenuate the habituation of HPA profile responses to repeated stress.

Early life exposure to specific environmental factors can contribute to development of behavioral disorders in adulthood. Although maternal high fat diet (HFD) consumption during the perinatal period has been reported to program offspring behavior, the underlying mechanisms remain to be elucidated. The present study was designed to evaluate the influence of maternal HFD on offspring behavior under nonstressed and stressful conditions, using male Sprague-Dawley offspring, which mothers were fed with HFD or normal diet (ND), receiving chronic unpredictable mild stress (CUMS) in the adulthood. We found that although the detrimental effects of maternal HFD consumption on offspring depressive behavior did not persist into adulthood, it markedly aggravated the behavioral disorder response to stressful challenge in adult offspring. Moreover, calcitonin gene-related peptide (CGRP) concentration in CSF and hippocampus were increased in the HFD + CUMS rats, compared to the ND + CUMS subjects. Another separate groups were fitted with intracerebroventricular (icv) cannulae. Central infusion of αCGRP8-37, a CGRP antagonist, produced antidepressant effects in HFD + CUMS rats, implying that the programming of maternal HFD on offspring behavior responses to stress may be mediated partially by endogenous central CGRP signaling. Moreover, we found that maternal HFD significantly exacerbated HPA profile response to acute restraint stress and attenuated the habituation of HPA responses to repeated restraint stress, suggesting that maternal HFD may program the changes of HPA-regulatory mechanisms. Overall, our findings suggest that maternal HFD influence adult depressive disorder response to stressful challenge, through the modulation of endogenous central CGRP signaling and HPA-regulatory components.