Chronological Molecular Changes in Neuronal Communication in Androgen-Deficient Rats

We investigated the early onset of molecular changes in the hippocampus of orchidectomy (ODX)-induced androgen-deficient rats. Transcript levels of the genes associated with loss of synaptic plasticity (Bdnf, Syn, GluN1, α7-nAChR, and M₁-mAChR), formation of neurofibrillary tangles (Tau4 and Tau3), and amyloid plaques (App, Adam10, and Bace1), in the hippocampus of rats at 0, 1, 3, 6, and 9 days after ODX (D₀, D₁, D₃, D₆ and D₉, respectively) were determined. Primarily, the sudden loss of androgen, as confirmed by the decreased serum testosterone levels and accessory sex organ weights, induced a chronological reduction in Syn (at D₁), and increase in GluN1 (at D₃), α7-nAChR, and M₁-mAChR (at D₆) and a decrease in Bdnf (at D₉) transcript levels. Tau4 and Tau3 mRNA levels were increased at D₆ and D₉, respectively. No changes in App, Adam10, and Bace1 mRNA levels were detected within the 9-day study period. To confirm those changes were caused by androgen deprivation and not increasing age, the mRNA expression levels of those genes in 9-day orchidectomized rats (ODX-D₉) were compared with age-matched intact rats. All changes of mRNA expression levels of the ODX-D₉ rats were aligned with the D₉ rats, except for GluN1 that was decreased in the ODX-D₉ rats. Moreover, the total and phosphorylated tau protein levels were increased in the ODX-D₉ rats. These results denote that androgen deficiency induces the early onset of neurodegeneration, while the loss of synaptic plasticity together with the formation of neurofibrillary tangles could be used as markers for neurodegenerative prediction.