Campêlo Clarissa L C, Santos José R, Silva Anatildes F, Dierschnabel Aline L, Pontes André, Cavalcante Jeferson S, Ribeiro Alessandra M, Silva Regina H
Memory Studies Laboratory, Department of Physiology, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
Laboratory of Behavioral and Evolutionary Neuroscience, Department of Bioscience, Universidade Federal de Sergipe, Itabaiana, SE, Brazil.
Behav Brain Res. 2017 Jun 15;328:138-148. doi: 10.1016/j.bbr.2017.04.028. Epub 2017 Apr 18.
Previous studies showed that the repeated administration with a low dose of reserpine (RES) induces a gradual appearance of motor signs and cognitive deficits compatible with parkinsonism in rodents. Environmental stimulation has neuroprotective effects in animal models of neurodegenerative damage, including acutely induced parkinsonism. We investigated the effects of exposure to an enriched environment (EE) on motor, cognitive and neuronal (levels of tyrosine hydroxylase, TH and brain derived neurotrophic factor, BDNF) deficits induced by a progressive model of Parkinson's disease (PD) in mice. Male mice were repeatedly treated with vehicle or 0.1mg/kg of RES (s.c) and kept under two housing conditions: standard environment (SE) and EE. In animals kept in SE, the treatment with RES induced deficits in motor function (catalepsy test, open field and oral movements), in novel object recognition (NOR) and plus-maze discriminative avoidance tasks. The environmental stimulation facilitated the recovery of motor deficits assessed by the catalepsy test after the end of treatment. Additionally, exposure to EE prevented the memory deficit in the NOR task. Treatment with RES induced a reduction in the number of TH positive cells in SNpc and VTA, which recovered 30days after the end of treatment. Finally, RES reduced the levels of BDNF in the striatum and the exposure to the EE prevented this effect. These results suggest that plastic brain changes induced by EE promote beneficial effects on the progression of neuronal impairment related to PD.
先前的研究表明，低剂量利血平（RES）反复给药会在啮齿动物中逐渐出现与帕金森病相符的运动症状和认知缺陷。环境刺激在神经退行性损伤的动物模型中具有神经保护作用，包括急性诱发的帕金森病。我们研究了暴露于丰富环境（EE）对小鼠帕金森病（PD）渐进模型诱导的运动、认知和神经元（酪氨酸羟化酶、TH和脑源性神经营养因子、BDNF水平）缺陷的影响。雄性小鼠反复接受载体或0.1mg/kg RES（皮下注射）治疗，并饲养在两种饲养条件下：标准环境（SE）和EE。在饲养于SE的动物中，RES治疗导致运动功能（僵住试验、旷场试验和口腔运动）、新物体识别（NOR）和加迷宫辨别回避任务出现缺陷。环境刺激促进了治疗结束后通过僵住试验评估的运动缺陷的恢复。此外，暴露于EE可预防NOR任务中的记忆缺陷。RES治疗导致黑质致密部（SNpc）和腹侧被盖区（VTA）中TH阳性细胞数量减少，治疗结束后30天恢复。最后，RES降低了纹状体中BDNF的水平，而暴露于EE可防止这种效应。这些结果表明，EE诱导的可塑性脑变化对与PD相关的神经元损伤进展具有有益影响。
