Inflammation Induced by Natural Neuronal Death and LPS Regulates Neural Progenitor Cell Proliferation in the Healthy Adult Brain

Inflammation is typically considered a negative response to injury or insult; however, recent advances demonstrate that inflammatory cells regulate development, plasticity, and homeostasis through anticytotoxic, progenerative responses. Here, we extend analyses of neuroinflammation to natural neurodegenerative and homeostatic states by exploiting seasonal plasticity in cytoarchitecture of the avian telencephalic song control nucleus, high vocal center [HVC (proper name)], in the songbird Gambel's white-crowned sparrow (Zonotrichia leucophrys gambelii). We report that local injection of the endotoxin lipopolysaccharide into HVC of birds in both breeding (high circulating testosterone level) and nonbreeding (low circulating testosterone level) conditions increased neural progenitor cell proliferation in the nearby but distinct ventricular zone. Additionally, we found that oral administration of the anti-inflammatory drug minocycline during seasonal regression of HVC reduced microglia activation in HVC and prevented the normal proliferative response in the ventricular zone to apoptosis in HVC. Our results suggest that local neuroinflammation positively regulates neural progenitor cell proliferation and, in turn, contributes to the previously described repatterning of HVC cytoarchitecture following seasonally induced neuronal loss.