The Protective Role of Perineuronal Nets Against Stress

Background The onset of psychiatric disorders, such as schizophrenia, anxiety, and depression, often occurs in late adolescence, a period when parvalbumin-positive interneurons (PVI) have not yet reached full maturity. Stress during this critical developmental window may lead to the functional loss of PVI in the ventral hippocampus (vHip), a phenomenon associated with these disorders. This vulnerability persists until the end of the critical period, marked by the appearance of perineuronal nets (PNNs)—a glycosaminoglycan matrix sheath that primarily surrounds PVI, stabilizing glutamatergic inputs to conclude the plastic phase while also protecting PVI from metabolic and oxidative damage. During adolescence, when PNNs are not yet fully developed, stress can have a more profound deleterious impact on PVI. Aims & Objectives The long-lasting effects of adolescent or adult stress on behavior, ventral tegmental area dopamine neuron activity, and the number of PVIs and their associated PNNs in the vHip were evaluated. We also tested whether PNN removal in the vHip of adult rats, proposed to reset PVIs to a juvenile-like state, would recreate an adolescent-like phenotype of stress susceptibility. Method Male rats underwent a 10-day stress protocol during adolescence or adulthood. Three to 4 weeks poststress, we evaluated behaviors related to anxiety, sociability, and cognition, ventral tegmental area dopamine neuron activity through in vivo electrophysiology, and the number of PV+ and PNN+ cells in the vHip. In addition, adult animals received intra-vHip infusion of ChABC (chondroitinase ABC) to degrade PNNs before undergoing stress. Results During this talk, we will discuss recent data showing that adolescent rats are more susceptible than adults to long-term abnormalities induced by stress. Interestingly, the removal of PNNs in the vHip of adult rats—an intervention proposed to reset PVI to a juvenile-like state—recreated an adolescent-like phenotype of stress susceptibility. Discussion & Conclusions Understanding the role of PNNs in shielding PVI from stress could inform strategies to mitigate PVI dysfunction and prevent the onset of psychiatric disorders.