Laboratory of Experimental and Computational Neuroscience, Department of Biosystems Engineering, Universidade Federal de São João del-Rei (UFSJ), São João del-Rei, MG, Brazil.
Neuroscience Discipline, Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM/UNIFESP), São Paulo, SP, Brazil; Centro de Neurociências e Saúde da Mulher "Professor Geraldo Rodrigues de Lima", Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM/UNIFESP), São Paulo, SP, Brazil.
Clinics (Sao Paulo). 2023 Jul 20;78:100242. doi: 10.1016/j.clinsp.2023.100242. eCollection 2023.
The 6-OHDA nigro-striatal lesion model has already been related to disorders in the excitability and synchronicity of neural networks and variation in the expression of transmembrane proteins that control intra and extracellular ionic concentrations, such as cation-chloride cotransporters (NKCC1 and KCC2) and Na+/K+-ATPase and, also, to the glial proliferation after injury. All these non-synaptic mechanisms have already been related to neuronal injury and hyper-synchronism processes.
The main objective of this study is to verify whether mechanisms not directly related to synaptic neurotransmission could be involved in the modulation of nigrostriatal pathways.
Male Wistar rats, 3 months old, were submitted to a unilateral injection of 24 µg of 6-OHDA, in the striatum (n = 8). The animals in the Control group (n = 8) were submitted to the same protocol, with the replacement of 6-OHDA by 0.9% saline. The analysis by optical densitometry was performed to quantify the immunoreactivity intensity of GFAP, NKCC1, KCC2, Na+/K+-ATPase, TH and Cx36.
The 6-OHDA induced lesions in the striatum, were not followed by changes in the expression cation-chloride cotransporters and Na+/K+-ATPase, but with astrocytic reactivity in the lesioned and adjacent regions of the nigrostriatal. Moreover, the dopaminergic degeneration caused by 6-OHDA is followed by changes in the expression of connexin-36.
The use of the GJ blockers directly along the nigrostriatal pathways to control PD motor symptoms is conjectured. Electrophysiology of the striatum and the substantia nigra, to verify changes in neuronal synchronism, comparing brain slices of control animals and experimental models of PD, is needed.
6-OHDA 黑质纹状体损伤模型已经与神经网络的兴奋性和同步性障碍以及控制细胞内外离子浓度的跨膜蛋白的表达变化有关，如阳离子-氯离子共转运蛋白（NKCC1 和 KCC2）和 Na+/K+-ATP 酶，并且，损伤后也与神经胶质细胞增殖有关。所有这些非突触机制都与神经元损伤和超同步过程有关。
本研究的主要目的是验证非突触神经递质传递机制是否可能参与黑质纹状体通路的调制。
雄性 Wistar 大鼠，3 个月大，在纹状体中接受单侧注射 24µg 6-OHDA（n=8）。对照组（n=8）的动物接受相同的方案，用 0.9%生理盐水代替 6-OHDA。通过光密度测定法进行分析，以定量 GFAP、NKCC1、KCC2、Na+/K+-ATP 酶、TH 和 Cx36 的免疫反应性强度。
6-OHDA 在纹状体中诱导的损伤不伴阳离子-氯离子共转运体和 Na+/K+-ATP 酶表达的变化，但伴有黑质纹状体损伤和邻近区域的星形胶质细胞反应性。此外，6-OHDA 引起的多巴胺能变性导致连接蛋白-36的表达变化。
推测使用 GJ 阻滞剂直接沿着黑质纹状体通路控制 PD 运动症状。需要对控制动物和 PD 实验模型的纹状体和黑质脑片进行电生理学研究，以验证神经元同步性的变化。
