Knowledge Bank

Chronic stress influences development and outcome of mood disorders in humans. Through the release of a myriad of inflammatory signals, chronic stress affects cognitive function, social behavior, and anxiety- and depression-like behaviors. In mice, repeated social defeat (RSD) has been shown to induce anxiety-like behavior and social withdrawal that is associated with a pro-inflammatory immune profile. One such change we documented, using Immunohistochemistry staining (IHC) was in the quantification of perineuronal nets (PNNs), an extracellular structure involved in stabilizing neuronal synapses. These nets showed an increase dependent on stress exposure in specific regions of the brain. Inclusion of PNN material has been found in microglia, suggesting the possibility of microglia mediated PNN formation. Here we administered PLX5622 to deplete microglia, which resulted in the depletion of PNNs in the RSD mouse model, supporting their potential involvement in PNN formation. Another route of PNN mediation was explored through IL-1 receptor-1 knockouts selectively in glutamatergic neurons. The IL-1 receptor is unique to the hippocampus and has been shown to be essential in neuronal sensitization. We showed that the absence of this receptor, and in turn its ability to sensitize neurons, reversed the PNN increase created through RSD in the dentate gyrus. To address PNN involvement in stress resultant behaviors, chondroitinase ABC (chABC) was administered through injection to the hippocampal region of the brain to enzymatically degrade perineuronal nets. The chABC enzyme did not effectively degrade the PNNs in our study, therefore deeming us unable to draw any conclusions about how their depletion impacts stress associated behavioral deficits. Ultimately, the expression of perineuronal nets may play a key role in the neuronal response to social stress.