Deletion of B-cell translocation gene 2 (BTG2) alters the responses of glial cells in white matter to chronic cerebral hypoperfusion.
Deletion of B-cell translocation gene 2 (BTG2) alters the responses of glial cells in white matter to chronic cerebral hypoperfusion.
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b细胞易位基因2 （BTG2）的缺失改变了白质胶质细胞对慢性脑灌注不足的反应。
DOI：
10.1186/s12974-021-02135-w
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发表时间：
2021-04-03
影响因子：
9.3
通讯作者：
Sato N
中科院分区：
文献类型：
--
作者：
Suzuki K;Shinohara M;Uno Y;Tashiro Y;Gheni G;Yamamoto M;Fukumori A;Shindo A;Mashimo T;Tomimoto H;Sato N
皮质下缺血性血管性痴呆是血管性痴呆的主要亚型之一，其特征在于慢性脑灌注不足引起的腔隙性梗死和白色病变。在这项研究中，我们使用了小鼠模型的双侧颈总动脉狭窄（BCAS），调查的作用，B细胞易位基因2（BTG 2），抗增殖基因，在白色胶质细胞反应慢性脑灌注不足。Btg2 −/−小鼠和同窝野生型对照小鼠接受BCAS或假手术。采用旷场实验和Morris水迷宫实验检测大鼠行为学表型。分析脑组织的白色病变和神经胶质变化的程度。为了进一步证实Btg2缺失对体外神经胶质细胞增殖的影响，在来自野生型和Btg2 −/−小鼠的混合神经胶质细胞中研究了BrdU掺入。与野生型小鼠相比，BCAS处理的Btg2 −/−小鼠表现出自发运动活动增加和空间学习能力较差。虽然BCAS后野生型和Btg2 −/−小鼠之间白色病变的严重程度没有显著差异，但BCAS治疗的Btg2 −/−小鼠视束白色物质中GFAP（星形胶质细胞的标志物）和Mac2（活化小胶质细胞和巨噬细胞的标志物）的免疫反应性高于BCAS治疗的野生型小鼠。在BCAS处理的Btg2 −/−小鼠中，GFAP的表达水平也显著升高。体外分析表明，Btg2 −/−小鼠中混合胶质细胞对与脑灌注不足相关的炎症刺激的反应中BrdU掺入量高于野生型小鼠。BTG2负调节胶质细胞增殖以响应脑灌注不足，导致行为改变。在线版本包含补充材料，可通过10.1186/s12974 - 021 - 02135-w获得。
Subcortical ischemic vascular dementia, one of the major subtypes of vascular dementia, is characterized by lacunar infarcts and white matter lesions caused by chronic cerebral hypoperfusion. In this study, we used a mouse model of bilateral common carotid artery stenosis (BCAS) to investigate the role of B-cell translocation gene 2 (BTG2), an antiproliferation gene, in the white matter glial response to chronic cerebral hypoperfusion. Btg2−/− mice and littermate wild-type control mice underwent BCAS or sham operation. Behavior phenotypes were assessed by open-field test and Morris water maze test. Brain tissues were analyzed for the degree of white matter lesions and glial changes. To further confirm the effects of Btg2 deletion on proliferation of glial cells in vitro, BrdU incorporation was investigated in mixed glial cells derived from wild-type and Btg2−/− mice. Relative to wild-type mice with or without BCAS, BCAS-treated Btg2−/− mice exhibited elevated spontaneous locomotor activity and poorer spatial learning ability. Although the severities of white matter lesions did not significantly differ between wild-type and Btg2−/− mice after BCAS, the immunoreactivities of GFAP, a marker of astrocytes, and Mac2, a marker of activated microglia and macrophages, in the white matter of the optic tract were higher in BCAS-treated Btg2−/− mice than in BCAS-treated wild-type mice. The expression level of Gfap was also significantly elevated in BCAS-treated Btg2−/− mice. In vitro analysis showed that BrdU incorporation in mixed glial cells in response to inflammatory stimulation associated with cerebral hypoperfusion was higher in Btg2−/− mice than in wild-type mice. BTG2 negatively regulates glial cell proliferation in response to cerebral hypoperfusion, resulting in behavioral changes. The online version contains supplementary material available at 10.1186/s12974-021-02135-w.
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影响因子：
5.3
作者：
Farioli-Vecchioli S;Ceccarelli M;Saraulli D;Micheli L;Cannas S;D'Alessandro F;Scardigli R;Leonardi L;Cinà I;Costanzi M;Mattera A;Cestari V;Tirone F
通讯作者：
Tirone F
影响因子：
3.8
作者：
Choi, Kyu-Sung;Kim, Ji Yeon;Lim, In Young
通讯作者：
Lim, In Young
影响因子：
3.6
作者：
DUBOIS, M;BOWMAN, PD;GOLDSTEIN, GW
通讯作者：
GOLDSTEIN, GW
影响因子：
4.6
作者：
Kaneko T;Sakuma T;Yamamoto T;Mashimo T
通讯作者：
Mashimo T
影响因子：
5.4
作者：
Konrad, MAP;Zúñiga-Pflücker, JC
通讯作者：
Zúñiga-Pflücker, JC