title: Evidence that microglia mediate the neurobiological effects of chronic psychological stress on the medial prefrontal cortex.
abstract: Psychological stress contributes to the development of clinical depression. This has prompted many preclinical studies to investigate the neurobiology of this relationship, however, the effects of stress on glia remain unclear. In this study, we wished to determine, first, how exposure to chronic psychological stress affects microglial activity within the prefrontal cortex (PFC) and, second, whether the observed changes were meaningfully related to corresponding changes in local neuronal activity and PFC-regulated behavior. Therefore, we examined markers of microglial activation, antigen presentation, apoptosis, and persistent neuronal activation within the PFC after exposure to repeated restraint stress. We also examined the effect of stress on spatial working memory, a PFC-dependent function. Finally, we tested the ability of a microglial activation inhibitor (minocycline) to alter the impact of chronic stress on all of these endpoints. Stressor exposure produced positively correlated increases in microglial and long-term neuronal activation in the PFC but not antigen presentation or apoptosis. As expected, it also impaired spatial working memory. Importantly, minocycline reduced the impact of stress on neuronal activation and working memory, as well as microglial activation. These results suggest a role for microglia in mediating the effects of stress on PFC neuronal function and PFC-regulated behavior.
authors: School of Biomedical Sciences and Pharmacy, Centre for Brain and Mental Health Research, University of Newcastle, New South Wales 2308, Australia.
authors: M
authors: M
authors: Hinwood
authors: J
authors: J
authors: Morandini
authors: T A
authors: TA
authors: Day
authors: F R
authors: FR
authors: Walker
mesh_terms: D000818:Animals; D002908:Chronic Disease; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D017628:Microglia / Q000473:pathology / Q000502:physiology*; D017397:Prefrontal Cortex / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013315:Stress, Psychological / Q000473:pathology / Q000503:physiopathology*