Synergistic effects of early life mild adversity and chronic social defeat on rat brain microglia and cytokines

•Mild early life stress primes microglia and alters its later response to stress.•Mild ELS reduces PPARγ expression in the hippocampus.•Mild ELS followed by CSD induces PPARγ expression in the hippocampus.•Chronic social defeat affects microglia in the amygdala.•CSD increases IL-1b and TNFα in the h...

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Published in:	Physiology & behavior Vol. 215; p. 112791
Main Authors:	Ferle, Vasiliki, Repouskou, Anastasia, Aspiotis, George, Raftogianni, Androniki, Chrousos, George, Stylianopoulou, Fotini, Stamatakis, Antonios
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-03-2020
Subjects:	Animals Brain - pathology Brain Chemistry Calcium-Binding Proteins - metabolism Child Child Abuse - psychology Chronic social defeat Cytokines - metabolism Early life stress Humans Iba-1 Interleukin-1beta - metabolism Male Maternal Deprivation Maze Learning Microfilament Proteins - metabolism Microglia Microglia - pathology Neuroinflammation PPAR gamma - metabolism PPARγ Psychological Distress Rats Social Defeat Tumor Necrosis Factor-alpha - metabolism CTR PBS MO TNFα DG PND Neuroinflammation IL-1β PFC AMY ELS PPARγ HIP Microglia DER Early life stress CSD BLA Chronic social defeat NGS Iba-1 RER
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Summary:	•Mild early life stress primes microglia and alters its later response to stress.•Mild ELS reduces PPARγ expression in the hippocampus.•Mild ELS followed by CSD induces PPARγ expression in the hippocampus.•Chronic social defeat affects microglia in the amygdala.•CSD increases IL-1b and TNFα in the hippocampus and the amygdala. Exposure to early life stress affects the development and function of the brain and when followed by adversities in adulthood, the negative effects of stress are enhanced. Microglia has been proposed as a potential mediator of this phenomenon. In the present study, we investigated the long-term effects of mild early life stress, the consequences of a stressor in adulthood as well as their interaction on microglial and cytokine (PPARγ, IL-1β and TNFα) levels in the brain of adult male rats. As an early life stress we used a model of maternal neglect, in which the dam is present but non-accessible to the pup for 15 min during postnatal days 10–13; as a stressor in adulthood we exposed animals to chronic social defeat (CSD) for 3 weeks. We determined in the hippocampus, prefrontal cortex and amygdala, the number of Iba-1+ microglial cells, the number of PPARγ+ cells as well as the relative expression of PPARγ, IL-1β and TNFα mRNA by qPCR. Following exposure to CSD, the number of Iba-1+ cells was increased in the hippocampus and the prefrontal cortex of adult animals exposed to mild early life stress, while in the absence of CSD no such difference was observed. Moreover, following CSD PPARγ levels were increased in the hippocampus of adult males exposed as neonates to “maternal neglect”. Our findings support the notion that early life stress, even a mild one, primes microglia and enhances its reactivity to a second stressful event, later in life, in accord with the “two-hit” hypothesis.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0031-9384 1873-507X
DOI:	10.1016/j.physbeh.2019.112791