Microglial responses to inflammatory challenge in adult rats altered by developmental exposure to polychlorinated biphenyls in a sex-specific manner

Polychlorinated biphenyls are ubiquitous environmental contaminants linkedc with peripheral immune and neural dysfunction. Neuroimmune signaling is critical to brain development and later health; however, effects of PCBs on neuroimmune processes are largely undescribed. This study extends our previo...

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Bibliographic Details
Published in:Neurotoxicology (Park Forest South) 2024-09, Vol.104, p.95-115
Main Authors: Walker, Katherine A., Rhodes, Simone T., Liberman, Deborah A., Gore, Andrea C., Bell, Margaret R.
Format: Article
Language:English
Subjects:
Endocrine-disrupting chemicals
Microglia
Neuroimmune
Polychlorinated biphenyls
Sex difference
Two-hit hypothesis
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Summary:Polychlorinated biphenyls are ubiquitous environmental contaminants linkedc with peripheral immune and neural dysfunction. Neuroimmune signaling is critical to brain development and later health; however, effects of PCBs on neuroimmune processes are largely undescribed. This study extends our previous work in neonatal or adolescent rats by investigating longer-term effects of perinatal PCB exposure on later neuroimmune responses to an inflammatory challenge in adulthood. Male and female Sprague-Dawley rats were exposed to a low-dose, environmentally relevant, mixture of PCBs (Aroclors 1242, 1248, and 1254, 1:1:1, 20 μg / kg dam BW per gestational day) or oil control during gestation and via lactation. Upon reaching adulthood, rats were given a mild inflammatory challenge with lipopolysaccharide (LPS, 50 μg / kg BW, ip) or saline control and then euthanized 3 hours later for gene expression analysis or 24 hours later for immunohistochemical labeling of Iba1+ microglia. PCB exposure did not alter gene expression or microglial morphology independently, but instead interacted with the LPS challenge in brain region- and sex–specific ways. In the female hypothalamus, PCB exposure blunted LPS responses of neuroimmune and neuromodulatory genes without changing microglial morphology. In the female prefrontal cortex, PCBs shifted Iba1+ cells from reactive to hyperramified morphology in response to LPS. Conversely, in the male hypothalamus, PCBs shifted cell phenotypes from hyperramified to reactive morphologies in response to LPS. The results highlight the potential for long-lasting effects of environmental contaminants that are differentially revealed over a lifetime, sometimes only after a secondary challenge. These neuroimmune endpoints are possible mechanisms for PCB effects on a range of neural dysfunction in adulthood, including mental health and neurodegenerative disorders. The findings suggest possible interactions with other environmental challenges that also influence neuroimmune systems. •Early PCB exposure alters neuroimmune responses to adult inflammatory challenge•PCBs alter Tlr4 and Nfkb gene expression responses to LPS independent of cytokines•PCBs alter hypothalamic dopamine, CRH, aromatase gene expression responses to LPS•PCBs shift microglial morphological responses to LPS in hypothalamus and PFC•PCB effects differed between sexes, brain regions, and from those at earlier ages
ISSN:0161-813X
1872-9711
1872-9711
DOI:10.1016/j.neuro.2024.07.009