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科学家揭示补体因子C1q在继发性脑损伤中的功能
作者:小柯机器人 发布时间:2021/9/12 12:56:53

美国加州大学Jeanne T. Paz团队近日取得一项新成果。经过不懈努力,他们发现补体因子C1q介导轻度脑损伤后睡眠纺锤波缺失和癫痫发生。相关论文于2021年9月10日发表在《科学》杂志上。

使用轻度创伤性脑损伤(mTBI) 小鼠模型,研究人员发现皮质-丘脑系统中C1q的表达会缓慢增加。C1q表达增加伴随着神经元丢失和慢性炎症的产生,并与睡眠纺锤波中断和癫痫活动的出现相关。阻断C1q消除了这些现象,表明C1q是mTBI后续疾病发生的调节因子。单核RNA测序表明小胶质细胞是丘脑C1q的来源。因此皮质丘脑回路可能成为治疗TBI相关疾病的新靶点。

据介绍,尽管TBI会严重破坏皮质,但大多数与TBI相关的缺陷则反映了随着时间推移而产生的继发性损伤。由于丘脑与皮质相连接,丘脑很可能是继发性损伤的产生部位。

附:英文原文

Title: Complement factor C1q mediates sleep spindle loss and epileptic spikes after mild brain injury

Author: Stephanie S. Holden, Fiorella C. Grandi, Oumaima Aboubakr, Bryan Higashikubo, Frances S. Cho, Andrew H. Chang, Alejandro Osorio Forero, Allison R. Morningstar, Vidhu Mathur, Logan J. Kuhn, Poojan Suri, Sethu Sankaranarayanan, Yaisa Andrews-Zwilling, Andrea J. Tenner, Anita Luthi, Eleonora Aronica, M. Ryan Corces, Ted Yednock, Jeanne T. Paz

Issue&Volume: 2021-09-10

Abstract: Although traumatic brain injury (TBI) acutely disrupts the cortex, most TBI-related disabilities reflect secondary injuries that accrue over time. The thalamus is a likely site of secondary damage because of its reciprocal connections with the cortex. Using a mouse model of mild TBI (mTBI), we found a chronic increase in C1q expression specifically in the corticothalamic system. Increased C1q expression colocalized with neuron loss and chronic inflammation and correlated with disruption in sleep spindles and emergence of epileptic activities. Blocking C1q counteracted these outcomes, suggesting that C1q is a disease modifier in mTBI. Single-nucleus RNA sequencing demonstrated that microglia are a source of thalamic C1q. The corticothalamic circuit could thus be a new target for treating TBI-related disabilities.

DOI: abj2685

Source: https://www.science.org/doi/10.1126/science.abj2685

 

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037