Colodete Débora A E, Grace Anthony A, Guimarães Francisco S, Gomes Felipe V
Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
Departments of Neuroscience, Psychiatry, and Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Biol Psychiatry Glob Open Sci. 2024 May 31;4(5):100338. doi: 10.1016/j.bpsgos.2024.100338. eCollection 2024 Sep.
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.
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.
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.
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.
精神疾病通常在青春期末期/成年早期出现，这一时期对社会环境因素的易感性增加，与小白蛋白中间神经元（PVI）发育不完全相吻合。这一时期的压力会导致腹侧海马体（vHip）中PVI的功能丧失，这与多巴胺系统过度活跃有关。这种易感性一直持续到PVI周围出现神经周网（PNN）。我们评估了青少年期或成年期压力对行为、腹侧被盖区多巴胺神经元活动以及vHip中PVI及其相关PNN数量的长期影响。此外，我们测试了在成年大鼠的vHip中去除PNN（这被认为可将PVI重置为类似幼年的状态）是否会重现应激易感性的青少年样表型。
雄性大鼠在青少年期或成年期接受为期10天的应激方案。应激后3至4周，我们评估了与焦虑、社交能力和认知相关的行为、腹侧被盖区多巴胺神经元活动以及vHip中PV和PNN细胞的数量。此外，成年动物在接受应激之前，接受vHip内注射软骨素酶ABC（ChABC）以降解PNN。
与成年期应激不同，青少年期应激会诱发焦虑反应、降低社交能力、导致认知缺陷、腹侧被盖区多巴胺系统过度活跃，并减少vHip中的PV和PNN细胞。然而，vHip内注射ChABC会使成年期应激产生与青少年期应激后观察到的类似变化。
我们的研究结果强调了青春期是一个对应激的长期影响高度敏感的时期，并突出了PNN对PVI应激诱导损伤的保护作用。
