Early life adversity in humans is linked to cognitive deficits and increased risk of mental illnesses, including depression, bipolar disorder, and schizophrenia, with evidence for different vulnerabilities in men versus women. Modeling early life adversity in rodents shows similar neuropsychological deficits that may partially be driven by sex-dependent dysfunction in parvalbumin (PV) interneurons in the prefrontal cortex (PFC), hippocampus (HPC), and basolateral amygdala (BLA). Research demonstrates that PV interneurons are particularly susceptible to oxidative stress; therefore, accumulation of oxidative damage may drive PV dysfunction following early life adversity. The goal of this study was to quantify oxidative stress accumulation in PV neurons in rats exposed to maternal separation (MS). Pups were separated from their dam and littermates for 4 hours per day from postnatal day (P)2 to 20. Serial sections from the PFC, HPC, and BLA of juvenile (P20) rats of both sexes were immunohistochemically stained with antibodies against PV and 8-oxo-dG, a marker for oxidative DNA damage. PV cell counts, colocalization with 8-oxo-dG, and intensity of each signal were measured in each region to determine the effects of MS and establish whether MS-induced oxidative damage varies between sexes. A significant increase in colocalization of PV and 8-oxo-dG was found in the PFC and HPC, indicating increased oxidative stress in that cell population following MS. Region-specific sex differences were also revealed in the PFC, BLA, and HPC. These data identify oxidative stress during juvenility as a potential mechanism mediating PV dysfunction in individuals with a history of early life adversity.
Copyright © 2020. Published by Elsevier B.V.