Early life stress by repeated maternal separation induces long-term neuroinflammatory response in glial cells of male rats

Abstract

Childhood maltreatment and neglect leads to a wide range of mental disorders highlighted by hormone and immune alterations in neglected children. This social-health challenge leads to the creation of early stress models such as maternal separation (MS) in rodents. We performed a MS model (4h per day, 21) (n=16 MS and n=16 control), and then measured three parameters in male rat adult brains, in order to look for long-term effects: GFAP-positive cells, which indicate astroglial changes, and Iba-1-positive cells, which inform us about reactive microglia and interleukin determination (IL-6, TNFα). These measurements were performed in prefrontal cortices, striatal areas, and the dorsal hippocampus. We found that MS produces a dramatic and sustained decrease in the astroglial population in all the areas measured, whereas microglial changes are more specific to striatal areas.

The Inflamed Brain in Schizophrenia: The Convergence of Genetic and Environmental Risk Factors That Lead to Uncontrolled Neuroinflammation

“…In humans and mice, ELS increases multiple blood proinflammatory markers including CRP, IL-1β, IL-6, IL-8, TNF-α (Hepgul et al, 2012;Marsland et al, 2017;Réus et al, 2017) while suppressing the anti-inflammatory cytokine IL-10, leading to depressive-like behaviors in mice (Réus et al, 2017). In line with these findings, ELS resulted in altered microglial gene expression, density, morphology and phagocytic activity during maturation in particular brain regions including the mPFC, striatum, anterior cingulate cortex and hippocampus (Cohen et al, 2016;Delpech et al, 2016;Bollinger et al, 2017;Wang et al, 2017;Banqueri et al, 2019;Réus et al, 2019). Chronic stress also altered microglial function by activating the P2X7 receptor, which induced the NLRP3 inflammasome thus increasing levels of mature IL-1β within the brain (Pan et al, 2014;Yue et al, 2017).…”

Microglial Function in the Effects of Early-Life Stress on Brain and Behavioral Development

“…In general, adult brains from MS mice do not present differences in the number of microglial cells, but show region-specific modulation in the expression of activation markers and phagocytic activity and motility. Specifically, MS induces long-term increases in the expression of IBA-1 in brain regions such as the PFC [61], the dorsal striatum, the nucleus accumbens, and the CA3 subregion of the HIP [63]. However, a decrease in IBA-1 expression was detected in the adult spinal cord from MS rats [64].…”

Long-Term Impact of Early-Life Stress on Hippocampal Plasticity: Spotlight on Astrocytes

“…The majority of studies investigating the impact of early life stress on astrocytes have focused on the expression of astrocyte-specific markers, such as glial fibrillary acid protein (GFAP) and the calcium binding protein S100ß in brain areas involved in emotional behavior control, while only a handful have assessed specific astrocytic functions (Table 1). Within the DH of adult rats, preexposure to MS reduced GFAP expression [124,125] or the number of GFAP(+) cells [126] in most studies (but see also [127]). A reduction of GFAP immunoreactivity was also observed after fractionated maternal care with the LNB protocol [128].…”

“…Within the DH of adult rats, preexposure to MS reduced GFAP expression [ 124 , 125 ] or the number of GFAP(+) cells [ 126 ] in most studies (but see also [ 127 ]). A reduction of GFAP immunoreactivity was also observed after fractionated maternal care with the LNB protocol [ 128 ].…”