Rodent models of Parkinson's disease: beyond the motor symptomatology.

Rodent models of Parkinson's disease: beyond the motor symptomatology.
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DOI:
10.3389/fnbeh.2013.00175
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发表时间:
2013
影响因子:
3
通讯作者:
Sousa N
Sousa N
中科院分区:
医学3区
文献类型:
--
作者:
Campos FL;Carvalho MM;Cristovão AC;Je G;Baltazar G;Salgado AJ;Kim YS;Sousa N

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帕金森病(PD)的典型特征是运动症状;然而,鉴于情绪(抑郁和焦虑)和认知的相关改变,非运动症状(NMS)越来越多地被认为与疾病状态相关。在此,特别是关于NMS,我们旨在比较三种PD动物模型的运动、情感和认知行为,这些模型触发两个大脑半球上的多巴胺能(DA能)变性:(i)6-羟基多巴胺(6-OHDA,8或6 μg)损伤模型;(ii)百草枯(PQ)诱导模型;和(iii)基于α-突触核蛋白过表达(α-syn)的遗传模型。6-将OHDA和α-syn载体双侧注射到成年雄性Wistar大鼠的黑质旁核(SNpc)中;至于PQ递送,将微渗透泵植入肩胛间区域。在所有模型中均观察到运动缺陷,SNpc中酪氨酸羟化酶阳性细胞的组织学分析显示所有动物模型中DA能神经元均显著丢失。此外,α-syn动物模型还表现出探索活动减少,6-OHDA和PQ动物表现出抑郁和焦虑样行为显著增加。有趣的是,仅在6-OHDA模型中观察到认知障碍(工作记忆)。总的来说,这些PD模型适合于模拟与PD相关的运动症状,每个模型都包含疾病的其他相关NMS组分,这些组分可能被证明有利于PD的进一步研究。
Parkinson's disease (PD) is classically characterized by motor symptoms; however, non-motor symptoms (NMS) are increasingly recognized as relevant in disease-state, given the associated alterations in mood (depression and anxiety) and cognition. Here, particularly in regards to NMS, we aimed to compare the motor, emotional and cognitive behavior of three animal models of PD that trigger dopaminergic (DAergic) degeneration on both brain hemispheres: (i) the 6-hydroxydopamine (6-OHDA, 8 or 6 μg) lesion model; (ii) the paraquat (PQ) induced model, and (iii) a genetic model based on α-synuclein overexpression (α-syn). 6-OHDA and α-syn vector were injected bilaterally in the substantia nigra pars compacta (SNpc) of adult male Wistar rats; as for PQ delivery, micro-osmotic pumps were implanted in the interscapular region. Motor deficits were observed in all models, with histological analysis of tyrosine hydroxylase positive cells in the SNpc revealing a significant loss of DAergic neurons in all animal models. In addition, the α-syn animal model also presented a reduction in exploratory activity, and the 6-OHDA and PQ animals displayed a significant increase in both depressive- and anxiety-like behavior. Interestingly, cognitive impairment (working memory) was only observed in the 6-OHDA model. Overall, these PD models are suitable for mimicking the motor symptoms associated to PD, with each encompassing other relevant NMS components of the disorder that may prove beneficial for further studies in PD.
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