INFLUENCE OF LIFESTYLE ON BRAIN SENSITIVITY TO CIRCULATING INSULIN-LIKE GROWTH FACTOR 1

Life style conditions such as social relationships and diet impinge on mood homeostasis, a mechanism that becomes dysregulated in high-incidence mental illnesses such as depression or Alzheimer’s dementia (AD). Since insulin-like growth factor 1 (IGF-1) modulates mood and its blood levels are altered both in AD and in affective disorders, we investigated whether its activity was altered in the brain of mice submitted to isolation or fed with a high-fat diet (HFD). As in humans, both life style conditions increased anxiety and depression-like behavior. Significantly, both life style conditions abrogated neuronal responses to systemic IGF-1. Thus, enhanced neuronal activity in response to intraperitoneal IGF-1, as determined by Ca ⁺⁺ fiber-photometry in the prefrontal cortex, was lost in isolated or HFD-fed mice. However, only the latter had elevated serum IGF-1 levels. These findings suggest that loss of brain IGF-1 input may contribute to mood disturbances observed in lonely and obese subjects. Furthermore, they provide additional insight into the heightened risk of depression and Alzheimer’s disease associated with these conditions. Importantly, since the reduction of IGF-1 activity in the brain is not consistently mirrored by its serum levels, serum measurements do not reliably reflect brain IGF-1 activity.