Chronic testosterone propionate supplement could activated the Nrf2-ARE pathway in the brain and ameliorated the behaviors of aged rats

• Antioxidant effect was studied by behavioral, biochemical and morphological methods.
• Balancing reactions and muscular strength performance were declined in aged rats.
• Nrf2 and Nrf2-dependent gene products were significantly decreased in aged rats.
• Testosterone propionate treatment ameliorate behaviors and activate Nrf2-ARE pathway.
• Testosterone propionate supplement protected TH-ir cells death in aged rats.

Aging is usually associated with a progressive disruption of the redox balance leading to recurrent damage resulting from oxidative stress. Oxidative stress resulting from excessive free-radical release is likely implicated in the initiation and progression of motor behavior disorders. Therefore, antioxidant therapies have received considerable attention in motor behavior defects treatment. The nuclear factor erythroid 2-related factor 2 (Nrf2) binds to antioxidant response element (ARE) to induce antioxidant and phase II detoxification enzymes under conditions of oxidative stress, which reduces oxidative stress and accumulation of toxic metabolites. Testosterone has many physiological and behavioral effects throughout the lifespan and shown to affect motor behavior in adult male rats and gonadectomized rats. However, whether Nrf2-ARE pathway is activated after testosterone administration has not been studied in aged rats. The tilting-plane test and the horizontal-wire test as well as the oxidative stress parameters, the expression of Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1) and the number of tyrosine hydroxylase immunoreactive (TH-ir) cells in brain were examined in aged rats following chronic subcutaneous injections of testosterone propionate (TP). Our study showed that chronic TP supplement significantly ameliorated the decline of balancing reactions and muscular strength associated with aging. Oxidative stress parameters were ameliorate, the expression of Nrf2, HO-1 and NQO1 at protein or gene levels and the number of TH-ir cells significantly increased in substantia nigra or caudate putamen after TP treatment in aged rats. Our findings demonstrated that chronic TP treatment activated Nrf2-ARE pathway may influence the maintenance of the balancing reactions and muscular strength and reduce TH-ir cells death in aged rats. Therefore, TP supplement have shown for therapeutic strategies in the treatment and modification of motor behavior disorders.