Sex-Specific Effects of Early Life Stress on Brain Mitochondrial Function, Monoamine Levels and Neuroinflammation

• Published in: Brain sciences Vol. 10; no. 7; p. 447
• Main Authors: Gonzalez-Pardo, Hector, Arias, Jorge L, Gomez-Lazaro, Eneritz, Taboada, Isabel Lopez, Conejo, Nelida M
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.07.2020; MDPI
• Subjects: Acids; Adults; Analysis; Animal behavior; Animal models; Brain; Child abuse & neglect; Chromatography; Cytochrome; cytochrome oxidase; cytokine; Cytokines; Demographic aspects; Dopamine; Energy; Energy metabolism; Females; Gender differences; Gene expression; Hippocampus; Histology; Inflammation; Influence; Interleukin 6; Males; maternal separation; Metabolism; Metabolites; Mitochondria; monoamine; Neostriatum; Neurophysiology; Norepinephrine; Nucleus accumbens; Oxidative stress; Physiological aspects; Prefrontal cortex; Rodents; Serotonin; sex; Sex differences; Sex differences (Psychology); Solvents; Stress (Psychology); Stress response; Tumor necrosis factor-α; Weaning; Spain
• ISSN: 2076-3425; 2076-3425
• DOI: 10.3390/brainsci10070447

Sex differences have been reported in the susceptibility to early life stress and its neurobiological correlates in humans and experimental animals. However, most of the current research with animal models of early stress has been performed mainly in males. In the present study, prolonged maternal separation (MS) paradigm was applied as an animal model to resemble the effects of adverse early experiences in male and female rats. Regional brain mitochondrial function, monoaminergic activity, and neuroinflammation were evaluated as adults. Mitochondrial energy metabolism was greatly decreased in MS females as compared with MS males in the prefrontal cortex, dorsal hippocampus, and the nucleus accumbens shell. In addition, MS males had lower serotonin levels and increased serotonin turnover in the prefrontal cortex and the hippocampus. However, MS females showed increased dopamine turnover in the prefrontal cortex and increased norepinephrine turnover in the striatum, but decreased dopamine turnover in the hippocampus. Sex differences were also found for pro-inflammatory cytokine levels, with increased levels of TNF-α and IL-6 in the prefrontal cortex and hippocampus of MS males, and increased IL-6 levels in the striatum of MS females. These results evidence the complex sex- and brain region-specific long-term consequences of early life stress.