Emerging roles for hypothalamic microglia as regulators of physiological homeostasis

The hypothalamus is a crucial brain region that responds to external stressors and functions to maintain physiological homeostatic processes, such as core body temperature and energy balance. The hypothalamus regulates homeostasis by producing hormones that thereby influence the production of other hormones that then control the internal milieu of the body. Microglia are resident macrophages and phagocytic immune cells of the central nervous system (CNS), classically known for surveying the brain’s environment, responding to neural insults, and disposing of cellular debris. Recent evidence has shown that microglia are also responsive to external stressors and can influence both the development and function of the hypothalamus in a sex-dependent manner. This emerging microglia-hypothalamic interaction raises the intriguing notion that microglia might play an unappreciated role in hypothalamic control of physiological homeostasis. In this review, we briefly outline how the hypothalamus regulates physiological homeostasis and then describe how this literature overlaps with our understanding of microglia’s role in the CNS. We also outline the current literature demonstrating how microglia loss or activation affects the hypothalamus, and ultimately homeostasis. We conclude by proposing how microglia could be key regulators of homeostatic processes by sensing cues external to the CNS and transmitting them through the hypothalamus.