Apoptosis in hippocampal tissue induced by oxidative stress in testosterone deprived male rats.

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.