Ghaffari-Nasab Arshad, Badalzadeh Reza, Mohaddes Gisou, Alipour Mohammad Reza
Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Exp Physiol. 2021 Jul;106(7):1621-1630. doi: 10.1113/EP089415. Epub 2021 Jun 4.
What is the central question of this study? Young plasma contains several rejuvenating factors that exert beneficial effects in ageing and neurodegenerative diseases: can repeated transfusion of young plasma improve depressive behaviour in aged rats? What is the main finding and its importance? Following chronic transfusion of young plasma, depressive behaviour was improved in the depression model of aged rats, which was associated with reduced apoptosis process in the prefrontal cortex.
Brain ageing alters brain responses to stress, playing an essential role in the pathophysiology of late-life depression. Moreover, apoptotic activity is up-regulated in the prefrontal cortex in ageing and stress-related mood disorders. Considerable evidence suggests that factors in young blood could reverse age-related dysfunctions in organs, especially in the brain. Therefore, this study investigated the effect of young plasma administration on depressive behaviours in aged rats exposed to chronic unpredictable mild stress (CUMS), with a focus on the apoptosis process. Young (3 months old) and aged (22 months old) male rats were randomly assigned into four groups: young control (YC), aged control (AC), aged rats subjected to CUMS (A+CUMS) and aged rats subjected to CUMS and treated with young plasma (A+CUMS+YP). In the A+CUMS and A+CUMS+YP groups, CUMS was used to generate the depression rat model. Moreover, the A+CUMS+YP group received pooled plasma (1 ml, intravenously), collected from young rats, three times per week for 4 weeks. Young plasma administration significantly improved CUMS-induced depression-like behaviours, including decreased sucrose consumption ratio, reduced locomotor activity and prolonged immobility time. Importantly, young plasma reduced neuronal apoptosis in the prefrontal cortex that was associated with reduced TUNEL-positive cells and cleaved caspase-3 protein levels in the A+CUMS+YP compared with the A+CUMS group. Young plasma can partially improve the neuropathology of late-life depression through the apoptotic signalling pathways.
本研究的核心问题是什么？年轻血浆含有多种在衰老和神经退行性疾病中发挥有益作用的年轻化因子：反复输注年轻血浆能否改善老年大鼠的抑郁行为？主要发现及其重要性是什么？在对老年大鼠进行慢性年轻血浆输注后，其抑郁行为在老年大鼠抑郁模型中得到改善，这与前额叶皮质中凋亡过程的减少有关。
大脑衰老会改变大脑对应激的反应，在晚年抑郁症的病理生理学中起重要作用。此外，在衰老和与应激相关的情绪障碍中，前额叶皮质的凋亡活性上调。大量证据表明，年轻血液中的因子可以逆转器官中与年龄相关的功能障碍，尤其是在大脑中。因此，本研究调查了年轻血浆给药对暴露于慢性不可预测轻度应激（CUMS）的老年大鼠抑郁行为的影响，重点关注凋亡过程。将年轻（3个月大）和老年（22个月大）雄性大鼠随机分为四组：年轻对照组（YC）、老年对照组（AC）、接受CUMS的老年大鼠（A+CUMS）和接受CUMS并接受年轻血浆治疗的老年大鼠（A+CUMS+YP）。在A+CUMS和A+CUMS+YP组中，使用CUMS建立抑郁大鼠模型。此外，A+CUMS+YP组每周静脉注射一次从年轻大鼠收集的混合血浆（1毫升），共4周，每周3次。给予年轻血浆显著改善了CUMS诱导的抑郁样行为，包括蔗糖消耗率降低、运动活动减少和不动时间延长。重要的是，与A+CUMS组相比，年轻血浆减少了前额叶皮质中的神经元凋亡，这与A+CUMS+YP组中TUNEL阳性细胞和裂解的caspase-3蛋白水平降低有关。年轻血浆可通过凋亡信号通路部分改善晚年抑郁症的神经病理学。
