%0 Journal Article
%T Degradation of Perineuronal Nets in the Ventral Hippocampus of Adult Rats Recreates an Adolescent-Like Phenotype of Stress Susceptibility.
%A Colodete DAE
%A Grace AA
%A Guimarães FS
%A Gomes FV
%J Biol Psychiatry Glob Open Sci
%V 4
%N 5
%D 2024 Sep
%M 39099729
暂无%R 10.1016/j.bpsgos.2024.100338
%X <B>UNASSIGNED: </B>Psychiatric disorders often emerge during late adolescence/early adulthood, a period with increased susceptibility to socioenvironmental factors that coincides with incomplete parvalbumin interneuron (PVI) development. Stress during this period causes functional loss of PVIs in the ventral hippocampus (vHip), which has been associated with dopamine system overdrive. This vulnerability persists until the appearance of perineuronal nets (PNNs) around PVIs. We assessed 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. Additionally, we 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.<BR><B>UNASSIGNED: </B>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, and the number of PV+ and PNN+ cells in the vHip. Furthermore, adult animals received intra-vHip infusion of ChABC (chondroitinase ABC) to degrade PNNs before undergoing stress.<BR><B>UNASSIGNED: </B>Unlike adult stress, adolescent stress induced anxiety responses, reduced sociability, cognitive deficits, ventral tegmental area dopamine system overdrive, and decreased PV+ and PNN+ cells in the vHip. However, intra-vHip ChABC infusion caused the adult stress to produce changes similar to the ones observed after adolescent stress.<BR><B>UNASSIGNED: </B>Our findings underscore adolescence as a period of heightened vulnerability to the long-lasting impact of stress and highlight the protective role of PNNs against stress-induced damage in PVIs.<BR>In this work, we aimed to go deeper into understanding perineuronal nets (PNNs), a specialized extracellular matrix that evolves and protects inhibitory neurons in the brain, specifically parvalbumin-positive interneurons (PVIs). PVIs are essential in regulating brain activity. PNNs only reach maturity in adulthood, which leaves these interneurons unprotected during early life. To investigate this vulnerability, we conducted experiments in which we exposed adolescent and adult animals to a stress protocol. We observed that adolescent animals exhibited a higher susceptibility to developing changes associated with psychiatric disorders later in life. This susceptibility may stem from the absence of PNN protection around their PVIs. To explore this possibility further, we administered an enzyme into a specific brain region, the ventral hippocampus, of adult animals to selectively remove PNNs and induce an adolescent-like state. When subjected to stress, these animals displayed abnormalities similar to those observed in animals stressed during adolescence. Our findings have significant implications, suggesting that the presence of PNN protection around PVIs may be critical for mitigating stress-related psychiatric disorders.