The Effect of Gestational Immune Activation on Estrogen Receptor Alpha Levels in the Medial Preoptic Area and Bed Nucleus of the Stria Terminalis of the Maternal Rat Brain

Abstract

Maternal Immune Activation (MIA) has been widely used as a model for the development of neurological disorders in offspring in large part due to the effect of neuroinflammation. Despite the multitude of research that explores direct effects on offspring, relatively little is known about the effects on the maternal brain. Studies have demonstrated that the frequency and quality of maternal care with which a mother provides her offspring can significantly affect the behavioral and neurological development of her offspring. Maternal behavior is primarily regulated by the action of estrogen with its nuclear receptor, ER-α, in key brain regions like the media preoptic area (MPOA) and bed nucleus of the stria terminalis (BNST). Furthermore, environmental enrichment (EE) has been shown to be neuroprotective following exposure to a stressor and is used as a model to counteract the deleterious effect of neuroinflammation. The question is then posed whether MIAinduced neuroinflammation has the capacity to cause a reduction in ER-α levels in the MPOA and BNST which could impact the quality of maternal care provided to offspring; moreover, does EE protect against this purported damage. Nulliparous female Sprague-Dawley rats housed in varying levels of environmental complexity were mated, and on gestational day 11, dams were administered an intraperitoneal injection of 100 µg/kg LPS or equivalent volume of saline. At postpartum day 21 dams were sacrificed, brains were collected and were prepared for immunohistochemical labeling of ER-α positive cells in the MPOA and BNST. MIA caused a significant decrease in ER-α in the BNST (but not the MPOA), a loss which was prevented in dams exposed to EE. These results suggest that MIA may negatively impact the maternal brain which can potentially result in altered levels of maternal care, ultimately affecting the development of offspring.