Adolescent stress sensitizes the adult neuroimmune transcriptome and leads to sex-specific microglial and behavioral phenotypes.

Autor: Bekhbat M; Department of Physiology, Emory University, Atlanta, GA, 30322, USA., Mukhara D; Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, 23298, USA., Dozmorov MG; Center for Clinical and Translational Research, Virginia Commonwealth University Medical Center, Richmond, VA, 23298, USA., Stansfield JC; Center for Clinical and Translational Research, Virginia Commonwealth University Medical Center, Richmond, VA, 23298, USA., Benusa SD; Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, 23298, USA., Hyer MM; Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, 23298, USA., Rowson SA; Department of Physiology, Emory University, Atlanta, GA, 30322, USA., Kelly SD; Department of Physiology, Emory University, Atlanta, GA, 30322, USA., Qin Z; Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA, USA., Dupree JL; Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, 23298, USA., Tharp GK; Division of Developmental & Cognitive Neuroscience, Yerkes National Primate Research Center, Atlanta, GA, 30322, USA., Tansey MG; Department of Physiology, Emory University, Atlanta, GA, 30322, USA., Neigh GN; Department of Physiology, Emory University, Atlanta, GA, 30322, USA. gretchen.mccandless@vcuhealth.org.; Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA, 23298, USA. gretchen.mccandless@vcuhealth.org.; Department of Psychiatry & Behavioral Sciences, Emory University, Atlanta, GA, 30322, USA. gretchen.mccandless@vcuhealth.org.
Jazyk: angličtina
Zdroj: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2021 Apr; Vol. 46 (5), pp. 949-958. Date of Electronic Publication: 2021 Feb 08.
DOI: 10.1038/s41386-021-00970-2
Abstrakt: Adolescent exposure to chronic stress, a risk factor for mood disorders in adulthood, sensitizes the neuroinflammatory response to a subsequent immune challenge. We previously showed that chronic adolescent stress (CAS) in rats led to distinct patterns of neuroimmune priming in adult male and female rats. However, sex differences in the neuroimmune consequences of CAS and their underlying mechanisms are not fully understood. Here we hypothesized that biological sex would dictate differential induction of inflammation-related transcriptomic pathways and immune cell involvement (microglia activation and leukocyte presence) in the hippocampus of male and female rats with a history of CAS. Adolescent rats underwent CAS (six restraint and six social defeat episodes during postnatal days 38-49), and behavioral assessments were conducted in adolescence and adulthood. Neuroimmune measures were obtained following vehicle or a systemic lipopolysaccharide (LPS) challenge in adulthood. CAS led to increased time in the corners of the open field in adolescence. In males, CAS also increased social avoidance. As adults, CAS rats displayed an exaggerated enrichment of the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway and chemokine induction following LPS challenge, and increased number of perivascular CD45 + cells in the hippocampus. However, CAS females, but not males, showed exaggerated glucocorticoid receptor (GR) pathway enrichment and increased microglial complexity. These results provide further insight to the mechanisms by which peripheral immune events may influence neuroimmune responses differentially among males and females and further demonstrate the importance of adolescent stress in shaping adult responses.
Databáze: MEDLINE
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