Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Biogerontology. 2023 Dec;24(6):957-969. doi: 10.1007/s10522-023-10056-9. Epub 2023 Aug 29.
Along with altering brain responses to stress, aging may also impair recovery from depression symptoms. In the present study, we investigated depressive-like behaviors in young and aged rats and assayed the levels of microRNA-101 (miR-101), Rac1/RhoA, PSD-95, and GluR1 in the prefrontal cortex (PFC) after stress cessation and after a recovery period. Young (3 months old) and aged (22 months old) male Wistar rats were divided into six groups; Young control (YNG), young rats received chronic stress for four weeks (YNG + CS), young rats received chronic stress for four weeks followed by a 6-week recovery period (YNG + CS + REC), Aged control (AGED), aged rats received chronic stress for four weeks (AGED + CS), and aged rats received chronic stress for four weeks followed by a 6-week recovery period (AGED + CS + REC). Stress-induced depression, evaluated by the sucrose preference test (SPT) and forced swimming test (FST), was yet observed after the recovery period in aged but not in young rats, which were accompanied by unchanged levels of miR-101, Rac1/RhoA, GluR1, and PSD-95 in the PFC of aged rats. These data suggested that impaired synaptic plasticity of glutamatergic synapses via the miR-101/Rac1/RhoA pathway may contribute to the delayed behavioral recovery after stress exposure observed in aging animals.
除了改变大脑对应激的反应外，衰老也可能损害抑郁症状的恢复。在本研究中，我们研究了年轻和老年大鼠的抑郁样行为，并检测了应激停止后和恢复期间前额叶皮层（PFC）中小鼠 miR-101（miR-101）、Rac1/RhoA、PSD-95 和 GluR1 的水平。年轻（3 个月大）和老年（22 个月大）雄性 Wistar 大鼠分为 6 组；年轻对照组（YNG），年轻大鼠接受为期 4 周的慢性应激（YNG+CS），年轻大鼠接受为期 4 周的慢性应激后进行 6 周的恢复期（YNG+CS+REC），老年对照组（AGED），老年大鼠接受为期 4 周的慢性应激（AGED+CS），以及老年大鼠接受为期 4 周的慢性应激后进行 6 周的恢复期（AGED+CS+REC）。通过蔗糖偏好测试（SPT）和强迫游泳测试（FST）评估应激诱导的抑郁，在恢复期后仍观察到老年大鼠中存在，但在年轻大鼠中不存在，老年大鼠 PFC 中的 miR-101、Rac1/RhoA、GluR1 和 PSD-95 水平没有变化。这些数据表明，通过 miR-101/Rac1/RhoA 通路谷氨酸能突触的突触可塑性受损可能导致衰老动物应激后观察到的行为恢复延迟。
