Maternal separation induces retinal and peripheral blood mononuclear cell alterations across the lifespan of female rats

Abstract

Early life stress alters the function and feedback regulation of the hypothalamic-pituitaryadrenal (HPA) axis, and can contribute to neuroinflammation and neurodegeneration by modifying peripheral blood mononuclear cell (PBMC) activity. The retina, as part of the nervous system, is sensitive to immune changes induced by stress. However, the consequences of stress experienced at an early age on retinal development have not yet been elucidated. Here we aimed to evaluate the impact of maternal separation (MatSep) across three stages of the lifespan (adolescent, adult, and aged) on the retina, as well as on progression through the cell cycle and mitochondrial activity in PBMCs from female Wistar rats. Newborn pups were separated from their mother from postnatal day (PND) 2 until PND 14 for 3 h/day. Retinal analysis from the MatSep groups showed architectural alterations such as a diminished thickness of retinal layers, as well as increased expression of proinflammatory markers DJ-1, Iba-1, and CD45 and the gliotic marker GFAP. Additionally, MatSep disrupted the cell cycle and caused long-term increases in mitochondrial activity in PBMCs from adolescent and adult rats. Changes in the cell cycle profile of the PBMCs from aged MatSep rats were undetected. However, these PBMCs exhibited increased sensitivity to H2O2-induced oxidative stress in vitro. Therefore, these results suggest that early life stress can have long-term effects on retinal structure and function, possibly elicited by neonatal immune preconditioning.