PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
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.
摘要：
精神病通常在青春期后期/成年早期出现，对社会环境因素敏感性增加的时期，与不完全的小白蛋白中间神经元（PVI）发育相吻合。在此期间的压力导致腹侧海马（vHip）中PVIs的功能丧失，与多巴胺系统超速有关。此漏洞一直存在，直到PVI周围出现神经周网(PNN)。我们评估了青少年或成人压力对行为的长期影响，腹侧被盖区多巴胺神经元活动，以及vHip中PVI及其关联的PNN的数量。此外,我们测试了成年大鼠vHip中是否去除PNN，提议将PVIs重置为类似少年的状态，会重现压力易感性的青春期表型。
■雄性大鼠在青春期或成年期接受10天的应激方案。压力过后三到四周,我们评估了与焦虑相关的行为，社交能力,和认知，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，成年动物在承受压力之前接受vHip内输注ChABC（软骨素酶ABC）以降解PNN。
■与成人压力不同，青少年压力诱发的焦虑反应，社交能力下降，认知缺陷,腹侧被盖区多巴胺系统过度驱动，vHip中PV+和PNN+细胞减少。然而,vHipChABC内输注导致成人压力产生类似于青春期压力后观察到的变化。
■我们的研究结果强调青春期是一个对压力的长期影响更加脆弱的时期，并强调了PNN对PVIs中压力引起的损害的保护作用。
在这项工作中,我们的目标是更深入地了解神经周网(PNN)，一种专门的细胞外基质，进化并保护大脑中的抑制性神经元，特别是小白蛋白阳性中间神经元（PVIs）。PVIs对调节大脑活动至关重要。PNN只有在成年后才能成熟，这使得这些中间神经元在生命早期得不到保护。要调查此漏洞，我们进行了实验,使青春期和成年动物暴露于应激方案.我们观察到，青春期动物在以后的生活中对与精神疾病相关的发展变化表现出更高的易感性。这种易感性可能源于其PVI周围缺乏PNN保护。为了进一步探索这种可能性，我们给大脑的特定区域注射了一种酶，腹侧海马体,成年动物选择性地去除PNN并诱导青春期样状态。当受到压力时，这些动物表现出与青春期压力动物相似的异常。我们的发现具有重要意义，提示PVIs周围PNN保护的存在对于缓解压力相关的精神疾病可能至关重要。
■雄性大鼠在青春期或成年期接受10天的应激方案。压力过后三到四周,我们评估了与焦虑相关的行为，社交能力,和认知，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，成年动物在承受压力之前接受vHip内输注ChABC（软骨素酶ABC）以降解PNN。
■与成人压力不同，青少年压力诱发的焦虑反应，社交能力下降，认知缺陷,腹侧被盖区多巴胺系统过度驱动，vHip中PV+和PNN+细胞减少。然而,vHipChABC内输注导致成人压力产生类似于青春期压力后观察到的变化。
■我们的研究结果强调青春期是一个对压力的长期影响更加脆弱的时期，并强调了PNN对PVIs中压力引起的损害的保护作用。
在这项工作中,我们的目标是更深入地了解神经周网(PNN)，一种专门的细胞外基质，进化并保护大脑中的抑制性神经元，特别是小白蛋白阳性中间神经元（PVIs）。PVIs对调节大脑活动至关重要。PNN只有在成年后才能成熟，这使得这些中间神经元在生命早期得不到保护。要调查此漏洞，我们进行了实验,使青春期和成年动物暴露于应激方案.我们观察到，青春期动物在以后的生活中对与精神疾病相关的发展变化表现出更高的易感性。这种易感性可能源于其PVI周围缺乏PNN保护。为了进一步探索这种可能性，我们给大脑的特定区域注射了一种酶，腹侧海马体,成年动物选择性地去除PNN并诱导青春期样状态。当受到压力时，这些动物表现出与青春期压力动物相似的异常。我们的发现具有重要意义，提示PVIs周围PNN保护的存在对于缓解压力相关的精神疾病可能至关重要。
