The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Activation and suppression of microglia during early development similarly disrupt neuroendocrine function in the female rat.   (#91)

Luba Sominsky 1 , Ilvana Ziko 1 , Alita Soch 1 , Simin Younesi 1 , Soniya Xavier 1 , Sarah J Spencer 1
  1. School of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia

Microglia, the major brain immune cells, play an important role in brain development. Early-life immune challenges that lead to long-term increases in microglial numbers and activity, induce a wide range of neuroendocrine abnormalities. Microglia are also activated in response to early-life and adult diet high and fat, with overfeeding and obesity having chronic neuroinflammatory effects. We have shown that rodents suckled in small litters, where they have greater access to their mother’s milk, maintain overweight throughout their life. These overweight rats have increased microglial proliferation and activation throughout the brain as early as postnatal day (P) 7, and these changes are maintained into adulthood. In females, these metabolic and neuroinflammatory changes are associated with a reduction in circulating gonadotropins, changes in ovarian follicle reserve, as well as changes in hypothalamic-pituitary-adrenal (HPA) axis activity, with reduced anxiety under non-stressed conditions, but increased central responsiveness to stress. Here, we investigated whether a suppression of microglia during early development, rather than its activation, can similarly induce neuroendocrine alterations in female rats. We used the Cx3cr1-Dtr rat model to investigate the long-term effects of acute microglial ablation on neuroendocrine end-points in females. Rat pups were administered with diphtheria toxin during critical time-points within the development of hypothalamic connectivity (P7) and immediately after its completion (P14). Our findings show microglial ablation on P7, but not P14, leads to a significant increase in adult body weight, reduction in circulating luteinising hormone (LH), reduction in basal release of adrenocorticotropic hormone (ACTH) and impacts on the ovarian follicle reserve. These findings suggest that both activation and suppression of microglia in early-life lead to long-term changes in neuroendocrine function impacting both the stress and reproductive axes. These data also indicate a critical time-window that occurs during hypothalamic development and when this region is more vulnerable to neuroinflammatory challenges.