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

Abstract

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.

Estrogen‐dependent sex difference in microglia in the developing brain of Japanese quail (Coturnix japonica)

“…In particular, it has been shown to both reduce microglial proliferation (Lenz et al., 2013; Tikka et al., 2001) and the iNOS expression in mammals (Amin et al., 1996; Buller et al., 2009; Yrjänheikki et al., 1998). Similarly, orally administered minocycline was recently shown to diminish microglial numbers in adult Gambel's white‐crowned sparrows (Larson et al., 2020). However, we did not find any effect of minocycline on the number of microglia, the number of microglia expressing iNOS and the expression of iNOS in embryonic quail.…”

“…The intensity of iNOS immunostaining, which reflects iNOS expression, does not differ between sexes, thus suggesting that female microglia may not be more active than those of males. Finally, the number of microglia and the intensity of iNOS immunofluorescence were not affected by minocycline, an antibiotic known to inhibit microglia in mammals and birds (Stirling et al., 2005; Tikka et al., 2001; Juha Yrjänheikki et al., 1999; Larson et al., 2020), suggesting that minocycline may not affect the developing bird microglia.…”

Microglia modulate proliferation, neurite generation and differentiation of human neural progenitor cells

“…Despite the fact that neural progenitor cells represent a cell type that has an essential role in neural development and regeneration, most studies published thus far are based on non-human mammalian, mainly rodent models ( Amato et al, 2011 ; Bi et al, 2014 ; Abbott and Nigussie, 2020 ; Larson et al, 2020 ). On the other hand, studies using NPCs of human origin mostly focused on their regenerative capacity for potential medical applications ( Nagoshi et al, 2019 ; Tsuji et al, 2019 ; Kajikawa et al, 2020 ).…”

Cd59 and inflammation orchestrate Schwann cell development

“…Interestingly, at sublytic levels, complement can stimulate SC and OLC proliferation in vitro without inducing cell death (Dashiell et al, 2000;Hila et al, 2001;Rus et al, 1997Rus et al, , 1996Tatomir et al, 2020). Complement is also a potent driver of inflammation, which is also known to drive cell proliferation (Kiraly et al, 2015;Larson et al, 2020;Morgan, 2016;Morgan and Harris, 2015;Silva et al, 2020). Although complement is present (Magdalon et al, 2020;Zhang and Cui, 2014), it is unclear if developmental levels of complement impact SC proliferation in vivo and whether this process is Cd59-dependent.…”