Laboratório de Neurotrauma e Biomarcadores, Departamento de Bioquímica, Programa de Pós-Graduação em Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil.
Laboratório de Neurotrauma e Biomarcadores, Departamento de Bioquímica, Programa de Pós-Graduação em Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil.
Toxicol Lett. 2019 Jun 1;307:72-80. doi: 10.1016/j.toxlet.2019.03.004. Epub 2019 Mar 8.
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.
我们假设，超生理剂量的合成代谢雄激素类固醇（AAS），如睾酮（TEST）和癸酸诺龙（NAND），可能会对突触和线粒体生物能量学的 extrasynaptic 成分产生不同的影响，从而导致记忆障碍。将油（VEH）、NAND 或 TEST（15mg/Kg）每天给雄性 CF-1 白化小鼠连续给药 19 天。我们评估了突触体和 extrasynaptic 线粒体中的 Ca 流入/流出、膜电位 ΔѰm、氧化呼吸状态、脱氢酶活性、HO 生成、Tau 磷酸化以及在 Morris 水迷宫（MWM）中的空间记忆。在突触体中，两种 AAS 都增加了 Ca 流入和 Na 依赖性外排。在 extrasynaptic 线粒体中，NAND 增加了 Ca 流入。NAND 明显损害了突触体和 extrasynaptic 线粒体中 ΔѰm 的形成和耗散，而 TEST 的影响则不那么明显。TEST 增加了突触体中的储备呼吸能力，而 NAND 降低了突触体和 extrasynaptic 线粒体中的脱氢酶活性。此外，NAND 增加了突触体和 extrasynaptic 线粒体的 HO 生成。NAND 增加了突触体中的 pTau。两种 AAS 均未在 MWM 上损害记忆表现。我们强调，高剂量的 NAND 会对突触和 extrasynaptic 线粒体生物能量学的成分产生神经毒性作用，如 Ca 流入、膜电位和 HO 生成。TEST 对突触和 extrasynaptic 线粒体生物能量学反应的神经毒性较小。
