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

Stress. 2019 Sep;22(5):563-570. doi: 10.1080/10253890.2019.1604666. Epub 2019 Apr 22.

Abstract

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.

Keywords: Astrocytes; GFAP; Iba-1; early life stress; maternal separation; microglia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Brain / metabolism
  • Dentate Gyrus / metabolism
  • Glial Fibrillary Acidic Protein
  • Gyrus Cinguli / metabolism
  • Hippocampus / metabolism
  • Inflammation / metabolism*
  • Male
  • Maternal Deprivation*
  • Microglia / metabolism
  • Neuroglia / metabolism*
  • Prefrontal Cortex / metabolism
  • Rats
  • Stress, Psychological / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Glial Fibrillary Acidic Protein
  • Tumor Necrosis Factor-alpha