Behavioral and Evolutionary Neurobiology Laboratory Department of Biosciences, Federal University of Sergipe, Itabaiana, SE, Brazil.
Department of Biosciences, Federal University of São Paulo, Santos, SP, Brazil.
J Chem Neuroanat. 2022 Nov;125:102162. doi: 10.1016/j.jchemneu.2022.102162. Epub 2022 Sep 14.
Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by progressive dopaminergic neuron loss. Animal models have been used to develop a better understanding of the pathophysiologic mechanisms of PD. However, these models are usually conducted with young animals diverging of the age of PD patients, suggesting a bias in translational science. Thus, the aim of the study was to evaluate the effect of the age on rats in a progressive parkinsonism model induced by reserpine (RES). Adult (6 - 8 month-old) or elderly (18 - 24 month-old) male rats were assigned to six groups: control-elderly (CTL-ELDERLY), reserpine-elderly (RES-ELDERLY), reserpine-elderly withdrawal (RES-ELDERLY WITHDRAWAL), control-adult (CTL-ADULT), reserpine-adult (RES-ADULT), and reserpine-adult withdrawal (RES-ADULT WITHDRAWAL). Animals received 15 injections every other day of RES (0.1 mg / kg) or vehicle during 30 days. Throughout treatment, animals were evaluated in the catalepsy test (every 48 h) and open field test (24 h after the second injection), and weight assessment (every 4 days) was also made. Upon completion of behavioral tests, rat brains were collected for tyrosine hydroxylase (TH) immunohistochemical analysis. Main results demonstrated that RES-treated animals spent more time in the catalepsy bar compared with control groups, moreover the RES-elderly group showed a longer catalepsy time compared with the RES-ADULT group. A shorter time from RES treatment to the development of symptoms was observed in the RES-ADULT group, compared with the RES-ELDERLY group. In addition, RES-induced weight loss in both RES-ELDERLY and RES-ADULT when compared with their corresponding controls. Cessation of RES treatment was followed by weight gain only in the RES-ADULT group. A significant decrease in TH-immunoreactive cells was observed in the substantia nigra pars compacta (SNpc) and dorsal striatum (STR) in the rats in both the RES-ADULT and RES-ELDERLY groups and in the ventral tegmental area in rats in the RES-ADULT group. Furthermore, TH immunoreactivity decrease was not reversible in SNpc and STR in the RES-ELDERLY. These results show that RES has an age-dependent effect in rats, suggesting a greater sensitivity of the dopaminergic pathway to RES with advancing age. These suggest that the RES rat model of parkinsonism can be useful in improving our knowledge on the effect of aging on neurodegeneration.
帕金森病（PD）是一种与年龄相关的神经退行性疾病，其特征是多巴胺能神经元进行性丧失。动物模型已被用于更好地了解 PD 的病理生理机制。然而，这些模型通常是在与 PD 患者年龄不同的年轻动物中进行的，这表明转化科学存在偏见。因此，本研究的目的是评估年龄对 RES 诱导的进行性帕金森病模型大鼠的影响。成年（6-8 月龄）或老年（18-24 月龄）雄性大鼠被分为六组：老年对照组（CTL-ELDERLY）、RES 老年组（RES-ELDERLY）、RES 老年停药组（RES-ELDERLY WITHDRAWAL）、成年对照组（CTL-ADULT）、RES 成年组（RES-ADULT）和 RES 成年停药组（RES-ADULT WITHDRAWAL）。动物在 30 天内每隔一天接受 15 次 RES（0.1mg/kg）或载体注射。在整个治疗过程中，每隔 48 小时对动物进行僵住测试，每隔 24 小时进行一次旷场测试，并每隔 4 天进行体重评估。行为测试完成后，收集大鼠大脑进行酪氨酸羟化酶（TH）免疫组织化学分析。主要结果表明，与对照组相比，RES 处理组动物在僵住杆上花费的时间更多，而 RES 老年组与 RES 成年组相比，僵住时间更长。与 RES-ELDERLY 组相比，RES-ADULT 组从 RES 治疗到症状出现的时间更短。与相应的对照组相比，RES 诱导的 RES-ELDERLY 和 RES-ADULT 体重减轻。RES-ADULT 组停药后仅出现体重增加。在 RES-ADULT 和 RES-ELDERLY 两组大鼠的黑质致密部（SNpc）和背侧纹状体（STR）以及 RES-ADULT 组大鼠的腹侧被盖区（VTA）中观察到 TH 免疫反应性细胞显著减少。此外，RES-ELDERLY 中 SNpc 和 STR 中的 TH 免疫反应性降低不可逆转。这些结果表明，RES 对大鼠具有年龄依赖性影响，表明多巴胺能通路对 RES 的敏感性随着年龄的增长而增加。这些表明，RES 帕金森病大鼠模型可用于提高我们对衰老对神经退行性变影响的认识。
