Critical roles of astrocytic-CCL2-dependent monocyte infiltration in a DJ-1 knockout mouse model of delayed brain repair.,Glia

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Critical roles of astrocytic-CCL2-dependent monocyte infiltration in a DJ-1 knockout mouse model of delayed brain repair.
Glia ( IF 5.4 ) Pub Date : 2020-03-16 , DOI: 10.1002/glia.23828
Dong-Joo Choi _{1,

2} , Hajie Yang _{1,

3} , Sushil Gaire _{1,

3,

4} , Keon Ah Lee _{1,

3} , Jiawei An _{1,

3,

4} , Byung Gon Kim _{2,

3,

4,

5} , Ilo Jou _{1,

2,

4} , Sang Myun Park _{1,

2,

4} , Eun-Hye Joe _{1,

2,

3,

4}

Affiliation

Monocyte‐derived macrophages play a role in the repair of the injured brain. We previously reported that a deficiency of the Parkinson's disease (PD)‐associated gene DJ‐1 delays repair of brain injury produced by stereotaxic injection of ATP, a component of damage‐associated molecular patterns. Here, we show that a DJ‐1 deficiency attenuates monocyte infiltration into the damaged brain owing to a decrease in C‐C motif chemokine ligand 2 (CCL2) expression in astrocytes. Like DJ‐1‐knockout (KO) mice, CCL2 receptor (CCR2)‐KO mice showed defects in monocyte infiltration and delayed recovery of brain injury, as determined by 9.4 T magnetic resonance imaging analysis and immunostaining for tyrosine hydroxylase and glial fibrillary acid protein. Notably, transcriptome analyses showed that genes related to regeneration and synapse formation were similarly downregulated in injured brains of DJ‐1‐KO and CCR2‐KO mice compared with the injured wild‐type brain. These results indicate that defective astrogliosis in DJ‐1‐KO mice is associated with decreased CCL2 expression and attenuated monocyte infiltration, resulting in delayed repair of brain injury. Thus, delayed repair of brain injury could contribute to the development of PD.

中文翻译：

星形细胞-CCL2 依赖性单核细胞浸润在延迟脑修复的 DJ-1 敲除小鼠模型中的关键作用。

单核细胞衍生的巨噬细胞在损伤大脑的修复中发挥作用。我们之前曾报道，帕金森病 (PD) 相关基因 DJ-1 的缺乏会延迟立体定向注射 ATP 产生的脑损伤的修复，ATP 是损伤相关分子模式的一个组成部分。在这里，我们表明，由于星形胶质细胞中 C-C 基序趋化因子配体 2（CCL2）表达减少，DJ-1 缺陷减弱了单核细胞浸润到受损大脑中。与 DJ-1-knockout (KO) 小鼠一样，CCL2 受体 (CCR2)-KO 小鼠显示出单核细胞浸润缺陷和脑损伤恢复延迟，通过 9.4 T 磁共振成像分析和酪氨酸羟化酶和胶质纤维酸蛋白的免疫染色确定. 尤其，转录组分析表明，与受伤的野生型大脑相比，DJ-1-KO 和 CCR2-KO 小鼠的受伤大脑中与再生和突触形成相关的基因同样下调。这些结果表明 DJ-1-KO 小鼠星形胶质细胞增生缺陷与 CCL2 表达降低和单核细胞浸润减弱有关，导致脑损伤修复延迟。因此，脑损伤的延迟修复可能有助于 PD 的发展。

更新日期：2020-03-16

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