6-Hydroxydopamine-Induced Lesions of Dopaminergic Neurons Alter the Function of Postsynaptic Cholinergic Neurons without Changing Cytoskeletal Proteins
6-Hydroxydopamine-Induced Lesions of Dopaminergic Neurons Alter the Function of Postsynaptic Cholinergic Neurons without Changing Cytoskeletal Proteins
复制标题
6-羟基多巴胺诱导的多巴胺能神经元损伤改变突触后胆碱能神经元的功能而不改变细胞骨架蛋白
作者：
N. Muma;John M. Lee;L. Gorman;B. Heidenreich;I. Mitrovic;T. Napier
许多神经退行性疾病的神经病理特征是含有细胞骨架蛋白的神经元内包涵体，如帕金森病中路易体中的神经丝和阿尔茨海默病中神经纤维缠结中的tau。阿尔茨海默病和帕金森病中也存在多巴胺和胆碱能系统的功能障碍。由于帕金森病的主要病理局限于多巴胺能系统，我们着手确定胆碱能系统的扰动是否是多巴胺能神经元丧失的结果。因此，在大鼠脑内微量注射6-羟基多巴胺后，用胆碱能终末区的半胆碱结合法检测胆碱能神经元的活动，并用免疫细胞化学方法检测多巴胺能神经元细胞骨架蛋白的扰动。注射6-羟基多巴胺显著减少了外侧中脑单胺能胞体的数量，并显著减少了多巴胺及其主要代谢产物在多巴胺能投射部位的数量。这种治疗增加了前额叶皮质(200%)和杏仁核(284%)的半羟基结合；然而，尽管先前有相反的报道，但对磷酸化神经细丝、微管相关蛋白(MAP)2、tau或成对螺旋丝(Phf)tau的免疫反应性没有增加。在将中等剂量的毒素直接注射到内侧前脑束或在脑室内注射高剂量毒素后，观察到细胞骨架蛋白的缺乏。这些结果表明，去掉前脑的多巴胺能输入会导致胆碱能系统的过度活动，但不足以诱导细胞骨架蛋白的突触后扰动，这种扰动发生在神经退行性疾病中。
The neuropathological hallmarks of many neurodegenerative diseases are intraneuronal inclusions containing cytoskeletal proteins such as neurofilaments in Lewy bodies in Parkinson's disease and tau in neurofibrillary tangles in Alzheimer's disease. Dysfunction in dopaminergic and cholinergic systems also exist in both Alzheimer's disease and Parkinson's disease. Because the primary pathology in Parkinson's disease is localized to the dopaminergic system, we set out to determine if perturbations in cholinergic systems are a consequence of dopaminergic neuron loss. Therefore, following intracerebral microinjections of 6-hydroxydopamine in rats, the activity of cholinergic neurons was measured by hemicholinium binding in cholinergic terminal fields and perturbations in cytoskeletal proteins were examined in dopaminoceptive neurons using immunocytochemistry. The 6-hydroxydopamine injections robustly reduced the number of monoaminergic cell bodies in the lateral midbrain and dramatically decreased dopamine and its major metabolites in dopaminergic projection sites. This treatment increased hemicholinium binding in the prefrontal cortex (200%) and amygdala (284%); however, despite previous reports to the contrary, there were no increases in immunoreactivity for phosphorylated neurofilaments, microtubule-associated protein (MAP) 2, tau or paired helical filament (PHF) tau. This lack of an increase in cytoskeletal proteins was observed following either injections of moderate doses of the toxin directly into the medial forebrain bundle or after high doses were administered intracerebroventricularly. These results suggest that removal of dopaminergic inputs to the forebrain results in hyperactivity of the cholinergic systems but is not sufficient to induce postsynaptic perturbations in cytoskeletal proteins which occur in neurodegenerative diseases.
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影响因子：
--
作者：
L. Záborszky;W. Cullinan;V. Luine
通讯作者：
L. Záborszky;W. Cullinan;V. Luine
DOI：
--
发表时间：
1987
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
G. Breese;G. Duncan;T. Napier;S. Bondy;L. Iorio;R. Mueller
通讯作者：
G. Breese;G. Duncan;T. Napier;S. Bondy;L. Iorio;R. Mueller
DOI：
10.1006/neur.1995.0016
发表时间：
1995-06-01
期刊：
NEURODEGENERATION
影响因子：
--
作者：
JEON, BS;JACKSONLEWIS, V;BURKE, RE
通讯作者：
BURKE, RE
影响因子：
2.5
作者：
BERGMAN, H;WICHMANN, T;DELONG, MR
通讯作者：
DELONG, MR
影响因子：
2.5
作者：
WICHMANN, T;BERGMAN, H;DELONG, MR
通讯作者：
DELONG, MR