Figure 1. Inflammation-mediated neurodegeneration in overnutrition-related diseases.

A. While majority of neurons in adult mammalian brain are terminally stable, a pool of neural cells including neurons undergoes slow-speed turnover in normal physiology, and this process requires neurogenesis induced by adult neural stem cells (NSCs) including hypothalamic NSCs, a small number of multipotent cells residing in several brain regions including the mediobasal hypothalamus. Although this NSCs-directed neurogenesis in physiological conditions is rather slow and also region-specific, recent research suggests that it may have important roles in maintaining the brain’s controls during life-long physiological homeostasis.

B. Under pathophysiological conditions such as long-term overnutrition and probably aging, the resulting neuroinflammation affects the turnover pool of neural cells in adult brain. This process involves the inhibitory action of neuroinflammation on survival and differentiation of NSCs, mediated by NF-κB-directed apoptosis and Notch signaling. The neurodegenerative change under these conditions is slow and modest; however, when it affects certain neuronal types which by nature have small populations but critical functions, it can have severe disease outcomes. For example, the impairment of NSCs in the mediobasal hypothalamus can lead to a factional reduction of hypothalamic POMC neurons over a long period and mediate a late-onset development of obesity and pre-diabetes.