Impaired mitochondrial function and abnormalities in the tryptophan (Trp)-kynurenine (Kyn) pathway are linked to age-related mood disorders. This study investigated the effect of intracerebroventricular (ICV) injection of the mitochondria isolated from young rat brain on depression-like behaviors of aged rats subjected to chronic mild stress (CMS). Aged (22 months old) male rats were randomly assigned into four groups: Aged, Aged + Mit, Aged + CMS, and Aged + CMS + Mit. Anxiety- and depression-like behaviors were assessed using elevated plus maze (EPM), open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT). Mitochondrial membrane potential (MMP), ATP levels, indoleamine 2, 3-dioxygenase (IDO) levels, and Kyn metabolites were measured in the prefrontal cortex (PFC). Golgi Cox staining was used to investigate the neuronal morphology. Mitotherapy decreased immobility time and anhedonia in the FST; increased open arm time and entries in the EPM; decreased grooming and increased rearing, center time, and the entrance in the OFT. Mitotherapy also reduced IDO and Kyn metabolites, restored MMP and ATP production, and enhanced dendritic length and spine density in the PFC. Overall, mitotherapy improved anxiety-and depression-like behaviors in aged rats and it could be considered as a new therapeutic strategy for age-related depressive disorders.

线粒体功能受损和色氨酸 (Trp)-犬尿氨酸 (Kyn) 通路异常与年龄相关的情绪障碍有关。本研究调查了脑室内 (ICV) 注射从年轻大鼠脑中分离的线粒体对慢性轻度应激 (CMS) 老年大鼠抑郁样行为的影响。将老年（22 个月大）雄性大鼠随机分为四组：老年组、老年组+Mit 组、老年组+CMS 组和老年组+CMS+Mit 组。使用高架十字迷宫 (EPM)、旷场测试 (OFT)、强迫游泳测试 (FST) 和蔗糖偏好测试 (SPT) 评估焦虑和抑郁样行为。在前额叶皮层 (PFC) 中测量线粒体膜电位 (MMP)、ATP 水平、吲哚胺 2、3-双加氧酶 (IDO) 水平和 Kyn 代谢物。高尔基 Cox 染色用于研究神经元形态。丝裂疗法减少了 FST 的不动时间和快感缺失；增加了 EPM 中的开放时间和条目；减少梳理，增加饲养、中心时间和 OFT 的入口。丝裂疗法还减少了 IDO 和 Kyn 代谢物，恢复了 MMP 和 ATP 的产生，并增强了 PFC 中的树突长度和脊柱密度。总体而言，丝裂疗法改善了老年大鼠的焦虑和抑郁样行为，可被视为治疗与年龄相关的抑郁症的新策略。恢复了 MMP 和 ATP 的产生，并增强了 PFC 中的树突长度和脊柱密度。总体而言，丝裂疗法改善了老年大鼠的焦虑和抑郁样行为，它可以被认为是治疗与年龄相关的抑郁症的新策略。恢复了 MMP 和 ATP 的产生，并增强了 PFC 中的树突长度和脊柱密度。总体而言，丝裂疗法改善了老年大鼠的焦虑和抑郁样行为，可被视为治疗与年龄相关的抑郁症的新策略。