Differential localization of α-, β- and γ-synucleins in the rat CNS

Differential localization of α-, β- and γ-synucleins in the rat CNS
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DOI:
10.1016/s0306-4522(02)00143-4
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发表时间:
2002-01-01
期刊:
影响因子:
3.3
通讯作者:
Dahlström, A
Dahlström, A
中科院分区:
医学3区
文献类型:
--
作者:
Li, JY;Jensen, PH;Dahlström, A

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α-突触核蛋白是一种突触前蛋白,通常参与突触囊泡的稳态。其基因中的错义突变导致蛋白质积极参与遗传形式的帕金森病的发展。此外,它的代谢在帕金森病的所有情况下都受到干扰,其中α-突触核蛋白以丝状形式积聚在路易体神经细胞病变中。路易体也在其他常见的神经退行性疾病中发展,如路易体痴呆和阿尔茨海默病的路易体变体。在本研究中,我们研究了α-,β-和γ-突触核蛋白在大鼠中枢神经系统中的详细分布。α-突触核蛋白在胞体中没有观察到,但在尾状核和壳核以及腹侧苍白球的神经末梢中有高强度的分布,而β-突触核蛋白在尾状核和壳核中的分布要弱得多,密度也较低。尾状核和壳核中未见γ-突触核蛋白。α-突触核蛋白在黑质网状部中分布很强,但在网状部神经元的胞体中非常弱或几乎不存在。相比之下,β-突触核蛋白在黑质中非常弱或不存在。在黑质网状部的终末中没有γ-突触核蛋白,但在黑质网状部中检测到稀疏分布的含有γ-突触核蛋白的神经元。在脑干中,α-突触核蛋白以及γ-突触核蛋白以高强度存在于蓝斑中,而β-突触核蛋白非常弱。此外,α-突触核蛋白在迷走神经核中是强的,但在眼神经核、面神经核、舌下神经核、附件核和模糊核中是弱的,其中β-突触核蛋白是非常强的。此外,γ-突触核蛋白定位于终端和细胞体的Edinger-Westphal核,红核,蓝斑,和大多数颅神经相关的核。在脊髓中,α-和γ-突触核蛋白强烈存在于板层I和11和在节前交感神经核,而β-突触核蛋白是非常weak.These结果表明,α-突触核蛋白是丰富的中央儿茶酚胺能区。β-突触核蛋白更多地定位于体细胞胆碱能成分中,而它在儿茶酚胺能神经元中特别弱或不存在。γ-突触核蛋白似乎存在于胆碱能和儿茶酚胺能区域中,但在前脑中非常弱。(C)2002年IBRO。由爱思唯尔科技有限公司出版。保留所有权利。
alpha-Synuclein is a presynaptic protein that normally participates in the homeostasis of synaptic vesicles. Missense mutations in its gene cause the protein to participate actively in the development of heritable forms of Parkinson's disease. Moreover, its metabolism is perturbed in all cases of Parkinson's disease where alpha-synuclein accumulates in a filamentous form in the Lewy body nerve cell lesion. Lewy bodies also develop in other common neurodegenerative disorders, like dementia with Lewy bodies and Lewy body variant of Alzheimer's disease. In the present study, we have studied the detailed distribution of alpha-, beta- and gamma-synuclein in the rat CNS.alpha-Synuclein was not observed in perikarya, but was distributed with high intensity in nerve terminals in the caudate and putamen and ventral pallidum, where beta-synuclein was much weaker and less densely distributed in the caudate and putamen. gamma-Synuclein was not found in the caudate and putatnen. alpha-Synuclein was robustly distributed in the substantia nigra pars reticulata, but was very weak or virtually absent from the perikarya of the neurons in the pars compacta. In contrast, beta-synuclein was very weak or absent from the substantia nigra. gamma-Synuclein was absent from the terminals of substantia nigra pars reticulata, but sparsely distributed gamma-synuclein-containing neurons were detected in the substantia nigra pars compacta. In the brainstem, alpha-synuclein as well as gamma-synuclein were present in the locus coeruleus with high intensity, while beta-synuclein was very weak. In addition, alpha-synuclein was intense in the vagus nucleus, but weak in the oculomotor, facial, hypoglossal, accessory and ambiguous nuclei, where beta-synuclein was very intensely present. Furthermore, gamma-synuclein was localized in the terminals and in cell bodies of the Edinger-Westphal nucleus, the red nucleus, locus coeruleus, and most cranial nerve-related nuclei. In the spinal cord, alpha- and gamma-synucleins were intensely present in laminae I and 11 and in the preganglionic sympathetic nuclei, whereas beta-synuclein was very weak.These results indicate that alpha-synuclein is abundant in central catecholaminergic regions. beta-Synuclein is more localized in the somatic cholinergic components, while it is particularly weak or absent from catecholaminergic neurons. gamma-Synuclein appears to be present in both cholinergic and catecholaminergic regions, but very weak in the forebrain. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved.