Sex-specific resilience of neocortex to food restriction
Mammals have evolved sex-specific adaptations to reduce energy usage in times of food scarcity. These adaptations are well described for peripheral tissue, though much less is known about how the energy-expensive brain adapts to food restriction, and how such adaptations differ across the sexes. Here, we examined how food restriction impacts energy usage and function in the primary visual cortex (V1) of adult male and female mice. Molecular analysis and RNA sequencing revealed that food restriction modulated canonical, energy-regulating pathways including oxidative phosphorylation, AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling, significantly in males but not in females V1. Moreover, we found that in contrast to males, food restriction in females non-significantly affected V1 ATP usage and visual coding precision (assessed by orientation selectivity). Decreased serum leptin is necessary for triggering energy-saving changes in male mouse V1 during food restriction. Consistent with this result, we found a significant decrease of serum leptin in food-restricted males but no significant change in food-restricted females. Collectively, our findings demonstrate that cortical function and energy usage in female mice are more resilient to food restriction than in males. The neocortex, therefore, contributes to sex-specific, energy-saving adaptations in response to metabolic challenge. Overall design: Primary visual cortex (V1) tissue was collected from adult male and female mice(7-9 weeks of age) that had either access to ad libitum food or were food restricted for 2-3 weeks to 85% of their baseline bodyweight prior to experimentation.  Mice were briefly anesthetized and decapitated and tissue snap-frozen. RNA isolation was performed and integrity confirmed (RIN>7) and samples were sent to Oxford genomics Centre for sequencing using Illumina NovaSeq6000