Astrocyte-secreted chordin-like 1 regulates spine density after ischemic injury.
Astrocyte-secreted chordin-like 1 regulates spine density after ischemic injury.
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DOI：
10.1038/s41598-022-08031-4
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发表时间：
2022-03-09
影响因子：
4.6
通讯作者：
Allen NJ
中科院分区：
文献类型：
--
作者：
Blanco-Suarez E;Allen NJ
缺血性损伤发生时，大脑的血液流动被剥夺，阻止细胞接受必需的营养。损伤核心是直接被剥夺并被梗死周围区域包围的脑区，这是一个具有恢复潜力的区域。在梗死周围区域，神经元发生树突棘的急性丢失，这改变了突触的可塑性并决定了神经元的存活。星形胶质细胞对缺血性损伤反应的保护或损害取决于具体的阶段，但我们对其潜在的机制缺乏明确的认识。chorordinlike 1 （Chrdl1）是一种星形胶质细胞分泌的蛋白，在小鼠视觉皮层中促进突触成熟并限制经验依赖的可塑性。鉴于这种可塑性限制功能，我们询问Chrdl1是否调节对缺血性损伤的反应，使用光血栓形成（PT）建模。我们发现，在pt后急性期和亚急性期，梗死周围星形细胞中的Chrdl1 mRNA均上调。为了确定增加的Chrdl1对PT反应的影响，我们分析了Chrdl1敲除小鼠。我们发现Chrdl1的缺失可以防止梗死周围区域缺血引起的脊柱丢失，减少核心细胞死亡，而不影响胶质细胞形成。这些发现突出了星形胶质细胞分泌蛋白在脑缺血损伤反应中调节结构可塑性的重要作用。
Ischemic injury occurs when the brain is deprived of blood flow, preventing cells from receiving essential nutrients. The injury core is the brain region directly deprived and is surrounded by the peri-infarct area, the region with recovery potential. In the peri-infarct area neurons undergo acute loss of dendritic spines, which modifies synaptic plasticity and determines neuronal survival. Astrocytes can be protective or detrimental to the ischemic injury response depending on the specific stage, yet we lack clear understanding of the underlying mechanisms. Chordin-like 1 (Chrdl1) is an astrocyte-secreted protein that promotes synaptic maturation and limits experience-dependent plasticity in the mouse visual cortex. Given this plasticity-limiting function we asked if Chrdl1 regulates the response to ischemic injury, modelled using photothrombosis (PT). We find that Chrdl1 mRNA is upregulated in astrocytes in the peri-infarct area in both acute and sub-acute phases post-PT. To determine the impact of increased Chrdl1 on the response to PT we analyzed Chrdl1 knock-out mice. We find that absence of Chrdl1 prevents ischemia-induced spine loss in the peri-infarct area and reduces cell death in the core, without impacting gliosis. These findings highlight the important role of astrocyte-secreted proteins in regulating structural plasticity in response to brain ischemic injuries.
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影响因子：
16.2
作者：
Berry KP;Nedivi E
通讯作者：
Nedivi E
DOI：
10.1111/j.1749-6632.2012.06668.x
发表时间：
2012-01-01
期刊：
THROMBOLYSIS AND ACUTE STROKE TREATMENT: PREPARING FOR THE NEXT DECADE
影响因子：
--
作者：
Heiss, Wolf-Dieter
通讯作者：
Heiss, Wolf-Dieter
影响因子：
8.3
作者：
Chang, CF;Lin, SZ;Wang, Y
通讯作者：
Wang, Y
影响因子：
16.2
作者：
Burda JE;Sofroniew MV
通讯作者：
Sofroniew MV
影响因子：
16.2
作者：
Espinosa JS;Stryker MP
通讯作者：
Stryker MP