Comparison of neuroprotective effects of dihydrotestosterone, 17β-estradiol, and Pueraria mirifica herb extract on cognitive impairment in androgen deficient male rats.

This study investigated the neuroprotective effects of dihydrotestosterone (DHT), 17β-estradiol (E2), and Pueraria mirifica herb extract (PME; an alternative source of natural estrogens) on the (i) learning and memory in androgen-deficient male rats, and on the hippocampus expression levels of (ii) mRNA of genes associated with synaptic transmission and structure, neurofibrillary tangles, and amyloid plaques, and (iii) total and phosphorylated tau proteins. The four-month-old male rats were sham-operated or orchidectomized (ODX). The ODX rats were divided into four groups, and orally treated for 2 months with either 1 mL/d of distilled water or 100 mg/kg/d of PME; or subcutaneously injected with 1 mg/kg/d of DHT or 80 μg/kg/d of E2. The impairment of spatial learning behavior and memory capacity in the ODX rats was prevented by DHT, E2, and PME. Recovery of the orchidectomy-induced deterioration of the synaptic plasticity in the hippocampus of rats was ranked as E2 ≥ PME > DHT. Both DHT and PME mitigated the increased Tau3 and Tau4 mRNA levels, and Tau-5 and P-Tau Ser396 protein levels more than E2 (DHT ≥ PME > E2). Only DHT tended to decrease App mRNA expression level. In conclusion, DHT showed a stronger efficacy for mitigation of the impaired spatial learning behavior and memory capacity in androgen-deficient male rats compared to E2 and PME, and their mechanisms of action are slightly different.