Anabolic-androgen steroids effects on bioenergetics responsiveness of synaptic and extrasynaptic mitochondria.

We hypothesized that supraphysiological administration of the anabolic-androgenic steroids (AAS) like testosterone (TEST) and nandrolone decanoate (NAND) might differentially affect synaptic and extrasynaptic components of mitochondrial bioenergetics, thereby resulting in memory impairment. Oil (VEH), NAND or TEST (15 mg/Kg) were daily administered to male CF-1 albino mice for 19-days. We evaluated in the synaptosomes and extrasynaptic mitochondria, Ca influx/efflux, membrane potential ΔѰm, oxidative respiratory states, dehydrogenases activity, HO production, Tau phosphorylation, and spatial memory in the Morris water maze (MWM). In synaptosomes, both AAS increased Ca influx and Na dependent efflux. In extrasynaptic mitochondria, NAND increased the Ca influx. NAND prominently impaired ΔѰm formation and dissipation in synaptosomal and extrasynaptic mitochondria, while the effect of TEST was less pronounced. TEST increased the Reserve Respiratory Capacity in synaptosomes, and NAND decreased dehydrogenases activity in synaptic and extrasynaptic mitochondria. Also, NAND increased HO production by synaptosomes and extrasynaptic mitochondria. NAND increased pTau in synaptosomes. Both AAS did not impair memory performance on MWM. We highlight that high doses of NAND cause neurotoxic effects to components of synaptic and extrasynaptic mitochondrial bioenergetics, like calcium influx, membrane potential and HO production. TEST was less neurotoxic to synaptic and extrasynaptic mitochondrial bioenergetics responses.