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

Childhood maltreatment and neglect lead to a wide range of mental disorders highlighted by hormone and immune alterations in neglected children. This social-health challenge has led to the creation of early stress models such as maternal separation (MS) in rodents. We performed a MS model (4 h per day, 21 days; n = 16 MS and n = 16 control), and then measured three parameters in adult male rat brains, in order to look for long-term effects of early life stress. We used immunocytochemistry to mark glial fibrillary acidic protein (GFAP)-positive cells, which indicates changes in astroglia, and ionized calcium binding adaptor molecule 1 (Iba-1)-positive cells, which inform about reactive microglia. In order to study mRNA levels of some immune mediators, interleukin determination (interleukin-6, IL-6; tumor necrosis factor, TNFα) mRNAs were evaluated by real-time polymerase chain reaction (rt-PCR) in discrete brain regions. Measurements of numbers of GFAP-positive cells, and expression of Iba-1, IL-6 and TNFα mRNAs were performed in prefrontal cortex (PFC): cingulate cortex (CG), prelimbic cortex (PL) and infralimbic cortex (IL), striatal areas (dorsal striatum, STD; and nucleus accumbens, ACC), and dorsal hippocampus (HC: CA1, CA3 and dentate gyrus (DG)). We found that MS produces a dramatic and sustained decrease in the astroglial population in all the areas measured (from -25% in CA1 to -85.7% in ACC), whereas increased numbers of microglia were found, in more restricted regions: STD (72.6%), ACC (31%) and CA3 (33.3%) areas. Regarding mRNA measurements, we found increased IL-6 mRNA expression in HC (104.2%), and after MS.