Acute social defeat-induced neuroinflammation in the vmPFC of Syrian hamsters via microglial activation

Research suggests causal relationships between neuroinflammation and stress-related psychopathologies. Exposure to moderate or chronic psychological stress in rodents leads to increased activation of microglia, the brain’s resident immune cells. The ventral medial prefrontal cortex (vmPFC) is a key limbic region involved in top-down regulation of psychological stress and mediates the deleterious effects of microglial activity following prolonged restraint stress. While there is a growing body of literature indicating that chronic social defeat increases microglial activity in the vmPFC, there has been little research investigating the effects of acute social defeat stress. Here, we used an acute social defeat paradigm in male Syrian hamsters consisting of three, 5-minute aggressive encounters in the home cages of a three, novel resident aggressors. 24-hours later, the effects of defeat-induced priming of ionized calcium-binding adaptor protein (Iba-1) expression, a microglial activation marker, was assessed by a subsequent exposure to 0, 20, 100, or 500 μg/kg (i.p.) injection of lipopolysaccharide (LPS). Four hours after injection, hamsters were euthanized, brains extracted, and expression of Iba-1 was later quantified via optical density and total pixel area measurements. In a subset of animals, administration of minocycline, a microglial activation inhibitor, was assessed to determine if blocking microglial activity in defeated animals will have functional behavioral consequences in a social interaction test and conditioned defeat test. 2x4 (stress x LPS) ANOVAs on optical density and total pixel area in the vmPFC suggest significant main effects of social defeat and LPS on both dependent measures. These results indicate that both acute social defeat and LPS treatment alter the activation of microglia in the vmPFC. Importantly, these data are the first to demonstrate that an acute stressor is capable of activating microglia in the vmPFC, which suggests that acute social defeat may prime vmPFC microglia to more rapidly display a phagocytic phenotype following an immune challenge.