Abstract

The testosterone decline is one of the potential causes of oxidative stress-induced anxiety and depressive behaviors, and cognitive impairment induces irreversible neuronal damage, which is not clearly understood. The orchidectomized rat model was used; the hippocampal neurons and anxiety behavior were analyzed. Adult male albino rats were divided into control and orchidectomy (ORX) groups, orchidectomy (ORX + T), and normal (Cont + T) groups. Testosterone propionate was used as a testosterone supplement. The anxiety and depressive-like behavior observed in ORX animals in the open field (OF) and elevated plus-maze experiments were effectively overturned in the ORX + T group. Studies on isolated hippocampus showed reduced antioxidant enzymes (SOD, CAT, and glutathione (GSH) compounds), increased lipid peroxidation (LPO), elevated caspase3, and reduced anti-apoptotic protein Bcl-2, and increased apoptotic nuclei in TUNEL staining of the hippocampus in the ORX rats. These observations indicate free radical-mediated neural damage. Testosterone presence promoted the antioxidant defense system and restored normal pyramidal neuron morphology in ORX + T. This study confirms that testosterone is indispensable in the normal adult hippocampus and deficiency seems to be a potential risk factor for neurodegenerative disorders. Besides, androgen appears to be a possible therapeutic strategy for treating depression/neurodegenerative diseases in aging men.

摘要

睾酮下降是氧化应激引起的焦虑和抑郁行为的潜在原因之一，认知障碍会引起不可逆的神经元损伤，这一点尚不清楚。使用兰花切除大鼠模型；分析海马神经元和焦虑行为。成年雄性白化大鼠分为对照组和兰花切除术（ORX）组、兰花切除术（ORX + T）和正常（Cont + T）组。丙酸睾酮用作睾酮补充剂。在开放场（OF）和高架十字迷宫实验中观察到的 ORX 动物中观察到的焦虑和抑郁样行为在 ORX + T 组中被有效地推翻。对孤立海马体的研究表明抗氧化酶（SOD、CAT 和谷胱甘肽 (GSH) 化合物）减少，脂质过氧化 (LPO) 增加，caspase3 升高，在 ORX 大鼠海马的 TUNEL 染色中，抗凋亡蛋白 Bcl-2 减少，凋亡细胞核增加。这些观察结果表明自由基介导的神经损伤。睾酮的存在促进了抗氧化防御系统并恢复了 ORX + T 中的正常锥体神经元形态。这项研究证实，睾酮在正常成人海马中是必不可少的，缺乏似乎是神经退行性疾病的潜在危险因素。此外，雄激素似乎是治疗老年男性抑郁症/神经退行性疾病的一种可能的治疗策略。睾酮的存在促进了抗氧化防御系统并恢复了 ORX + T 中的正常锥体神经元形态。这项研究证实，睾酮在正常成人海马中是必不可少的，缺乏似乎是神经退行性疾病的潜在危险因素。此外，雄激素似乎是治疗老年男性抑郁症/神经退行性疾病的一种可能的治疗策略。睾酮的存在促进了抗氧化防御系统并恢复了 ORX + T 中的正常锥体神经元形态。这项研究证实，睾酮在正常成人海马中是必不可少的，缺乏似乎是神经退行性疾病的潜在危险因素。此外，雄激素似乎是治疗老年男性抑郁症/神经退行性疾病的一种可能的治疗策略。