Differential Regional Responses in Soluble Monomeric Alpha Synuclein Abundance Following Traumatic Brain Injury.
Differential Regional Responses in Soluble Monomeric Alpha Synuclein Abundance Following Traumatic Brain Injury.
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创伤性脑损伤后可溶性单体α突触核蛋白丰度的不同区域反应。
DOI：
10.1007/s12035-020-02123-w
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发表时间：
2021-01
影响因子：
5.1
通讯作者：
Dixon CE
中科院分区：
文献类型：
--
作者：
Carlson SW;Yan HQ;Li Y;Henchir J;Ma X;Young MS;Ikonomovic MD;Dixon CE
α-突触核蛋白（α-synuclein）是一种主要存在于突触前末梢的神经元蛋白。虽然α-突触核蛋白聚集体的病理学作用一直是几种神经退行性疾病中深入研究的主题，但对单体α-突触核蛋白的变化和对神经元功能的相关生理学后果的关注较少。越来越多的证据支持α-突触核蛋白在神经传递中的重要生理作用。在创伤性脑损伤（TBI）的背景下，我们假设可溶性单体α-突触核蛋白的区域丰度在损伤后的慢性时间段内发生改变。为此，我们在控制性皮质撞击（CCI）损伤后6小时、1天、1周、2周、4周和8周评估了成年大鼠皮质、海马和纹状体中的α-突触核蛋白。Western blot分析表明，与假手术动物相比，CCI后6小时、1天、1、2和8周时同侧海马中单体α-突触核蛋白水平降低，CCI后1周和2周时同侧皮质中单体α-突触核蛋白水平降低，CCI后6小时时同侧纹状体中单体α-突触核蛋白水平降低。免疫组织化学分析显示，CCI后1周，与假手术动物相比，同侧海马中α-突触核蛋白较低，突触素染色适度减少，没有细胞内或细胞外α-突触核蛋白聚集的证据。总的来说，这些发现表明海马中单体α-突触核蛋白的蛋白丰度在广泛的（急性至慢性）损伤后间隔内减少。这种缺陷可能导致TBI后发生的慢性神经传递受损。
Alpha synuclein (α-synuclein) is a neuronal protein found predominately in pre-synaptic terminals. While the pathological effects of α-synuclein aggregates has been a topic of intense study in several neurodegenerative conditions, less attention has been placed on changes in monomeric α-synuclein and related physiological consequences on neuronal function. A growing body of evidence supports an important physiological role of α-synuclein in neurotransmission. In the context of traumatic brain injury (TBI), we hypothesized that the regional abundance of soluble monomeric α-synuclein is altered over a chronic time period post-injury. To this end, we evaluated α-synuclein in the cortex, hippocampus and striatum of adult rats at 6 hours, 1 day, 1, 2, 4, and 8 weeks after controlled cortical impact (CCI) injury. Western blot analysis demonstrated decreased levels of monomer α-synuclein protein in the ipsilateral hippocampus at 6 hours, 1 day, 1, 2 and 8 weeks, as well as in the ipsilateral cortex at 1 and 2 weeks and in the ipsilateral striatum at 6 hours after CCI compared to sham animals. Immunohistochemical analysis revealed lower α-synuclein and a modest reduction in synaptophysin staining in the ipsilateral hippocampus at 1 week after CCI compared to sham animals, with no evidence of intracellular or extracellular a-synuclein aggregates. Collectively, these findings demonstrate that monomeric α-synuclein protein abundance in the hippocampus is reduced over an extensive (acute-to-chronic) post-injury interval. This deficit may contribute to the chronically impaired neurotransmission known to occur after TBI.
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影响因子：
16.6
作者：
Choi, Insup;Zhang, Yuanxi;Yue, Zhenyu
通讯作者：
Yue, Zhenyu
影响因子：
81.5
作者：
Blennow, Kaj;Brody, David L.;Zetterberg, Henrik
通讯作者：
Zetterberg, Henrik
影响因子：
5.3
作者：
Albensi, BC;Sullivan, PG;Mattson, MP
通讯作者：
Mattson, MP
鉴定与单体和寡聚 α-突触核蛋白结合的突触体蛋白。
影响因子：
3.7
作者：
Betzer C;Movius AJ;Shi M;Gai WP;Zhang J;Jensen PH
通讯作者：
Jensen PH
影响因子：
3.4
作者：
Carlson SW;Henchir J;Dixon CE
通讯作者：
Dixon CE