Developmental Effects of Maternal Separation on Oxidative Stress Accumulation in Fast-Spiking Parvalbumin Neurons in Prefrontal Cortex of Male and Female Rats

Presenter: Alexa Soares

Research Category: Physical and LIfe Sciences
Additional Authors: Kelsea Gildawie, Jennifer Honeycutt, Heather Brenhouse
PI: Heather Brenhouse
Award Winner Category: Sail Award

Early life adversity in humans is linked to cognitive deficits and increased risk of mental illnesses, including depression, bipolar disorder, and schizophrenia. 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). Research demonstrates that PV interneurons are particularly susceptible to oxidative stress, so the accumulation of oxidative damage may be driving PV dysfunction following early life adversity.

The goal of this study was to quantify oxidative stress accumulation in PV neurons in the PFC of rats exposed to maternal separation (MS). To do this, pups were separated from their dam for 4 hours per day from postnatal day (P)2 to 20. Serial sections from the prelimbic (PL) and infralimbic (IL) PFC of juvenile (P20) and adolescent (P40) rats of both sexes were immunohistochemically stained with antibodies against PV, as well as 8-oxo-dG, a marker for oxidative DNA damage. Colocalization was measured in the PFC to determine the oxidative effect of MS and establish whether its progression varies between sexes. A significant increase in colocalization of PV and 8-oxo-dG was found in the PL of juvenile rats, indicating increased oxidative stress immediately following MS.

Additionally, sex differences in PV cell count was found in both the PL and IL of adolescent rats. These data identify a potential timepoint at which antioxidant treatment may be administered in order to prevent further neurological dysfunction in individuals subject to early life adversity.