Institute of Neurology (Edinger Institute), University Hospital, Goethe University, Frankfurt am Main, Germany.
Institute of Pathophysiology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
PLoS Biol. 2020 Mar 16;18(3):e3000643. doi: 10.1371/journal.pbio.3000643. eCollection 2020 Mar.
Communication with the hematopoietic system is a vital component of regulating brain function in health and disease. Traditionally, the major routes considered for this neuroimmune communication are by individual molecules such as cytokines carried by blood, by neural transmission, or, in more severe pathologies, by the entry of peripheral immune cells into the brain. In addition, functional mRNA from peripheral blood can be directly transferred to neurons via extracellular vesicles (EVs), but the parameters that determine their uptake are unknown. Using varied animal models that stimulate neuronal activity by peripheral inflammation, optogenetics, and selective proteasome inhibition of dopaminergic (DA) neurons, we show that the transfer of EVs from blood is triggered by neuronal activity in vivo. Importantly, this transfer occurs not only in pathological stimulation but also by neuronal activation caused by the physiological stimulus of novel object placement. This discovery suggests a continuous role of EVs under pathological conditions as well as during routine cognitive tasks in the healthy brain.
与造血系统的交流是调节健康和疾病中大脑功能的一个重要组成部分。传统上，人们认为这种神经免疫通讯的主要途径是通过血液中的单个分子（如细胞因子），通过神经传递，或者在更严重的病理情况下，通过外周免疫细胞进入大脑。此外，外周血中的功能性 mRNA 可以通过细胞外囊泡（EVs）直接转移到神经元中，但决定其摄取的参数尚不清楚。我们使用不同的动物模型，通过外周炎症、光遗传学和选择性蛋白酶体抑制多巴胺（DA）神经元来刺激神经元活动，结果表明 EV 从血液中的转移是由体内神经元活动触发的。重要的是，这种转移不仅发生在病理性刺激中，也发生在由新物体放置引起的生理刺激引起的神经元激活中。这一发现表明，EV 在病理条件下以及在健康大脑的常规认知任务中都发挥着持续的作用。
