瑞典林雪平大学David Engblom研究组发现，小胶质细胞激活通过前列腺素介导的纹状体神经元调节而引起负面情绪。该研究于2021年1月20日在线发表于国际一流学术期刊《免疫》。

为了研究小胶质细胞信号如何调节情绪，研究人员使用了小鼠小胶质细胞活性的双向化学遗传学操纵。小胶质细胞在背侧纹状体中的激活诱导局部细胞因子的表达和以情绪低下和厌恶为特征的负性情感状态，而小胶质细胞的失活则阻止了由全身性炎症引起的厌恶。小胶质细胞中白介素6信号传导和环加氧酶1介导的前列腺素合成对于炎症诱导的厌恶至关重要。

相应地，小胶质细胞激活导致纹状体神经元兴奋性的前列腺素依赖性降低。这些发现表明，小胶质细胞活化通过前列腺素依赖性纹状体神经元的调节引起负面情绪，并表明对该机制的干扰可以减轻小胶质细胞活化相关的躯体和精神疾病的抑郁症状。

据悉，小胶质细胞在许多神经系统疾病中被激活，并被认为在包括重度抑郁症在内的情感疾病进展中起着重要作用。

附：英文原文

Title: Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons

Author: Anna M. Klawonn, Michael Fritz, Silvia Castany, Marco Pignatelli, Carla Canal, Fredrik Simil, Hugo A. Tejeda, Julia Levinsson, Maarit Jaarola, Johan Jakobsson, Juan Hidalgo, Markus Heilig, Antonello Bonci, David Engblom

Issue&Volume: 2021-01-20

Abstract: Microglia are activated in many neurological diseases and have been suggested to playan important role in the development of affective disorders including major depression.To investigate how microglial signaling regulates mood, we used bidirectional chemogeneticmanipulations of microglial activity in mice. Activation of microglia in the dorsalstriatum induced local cytokine expression and a negative affective state characterizedby anhedonia and aversion, whereas inactivation of microglia blocked aversion inducedby systemic inflammation. Interleukin-6 signaling and cyclooxygenase-1 mediated prostaglandinsynthesis in the microglia were critical for the inflammation-induced aversion. Correspondingly,microglial activation led to a prostaglandin-dependent reduction of the excitabilityof striatal neurons. These findings demonstrate a mechanism by which microglial activationcauses negative affect through prostaglandin-dependent modulation of striatal neuronsand indicate that interference with this mechanism could milden the depressive symptomsin somatic and psychiatric diseases involving microglial activation.

DOI: 10.1016/j.immuni.2020.12.016

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30544-6