小柯机器人

2021年6月30日，美国加州理工学院Wei-Li Wu等研究人员在《自然》杂志发表论文。该研究发现，微生物群通过大脑中的压力反应神经元来调节社会行为。

研究人员表明，微生物组能够调节雄性小鼠特定大脑区域的神经元活动，进而调节典型的压力反应和社会行为。无菌和抗生素治疗小鼠的社会偏差与应激激素皮质酮水平升高有关，皮质酮主要由激活下丘脑-垂体-肾上腺（HPA）轴产生。肾上腺切除术、糖皮质激素受体拮抗剂或皮质酮合成的药理学抑制可有效纠正微生物组耗竭后的社会缺陷。特定大脑区域中糖皮质激素受体的遗传敲除或下丘脑室旁核中产生促肾上腺皮质激素释放激素（CRH）的神经元的化学失活可逆转抗生素治疗小鼠的社会障碍。

相反，室旁核中表达CRH 的神经元特异性激活会导致微生物群正常的小鼠出现社交缺陷。通过微生物组分析和体内选择，研究人员确定了一种细菌物种——粪肠球菌，它促进社交活动并降低社交压力后小鼠的皮质酮水平。

这些研究表明，特定的肠道细菌可以抑制HPA轴的激活，并表明微生物组可以通过介导大脑压力反应的离散神经元回路来影响社会行为。

据了解，动物之间的社交互动会调节基本行为，包括交配、养育和防御。肠道微生物群有助于小鼠的社交活动，但调节这种复杂行为的肠脑连接及其潜在的神经基础尚不清楚。

附：英文原文

Title: Microbiota regulate social behaviour via stress response neurons in the brain

Author: Wei-Li Wu, Mark D. Adame, Chia-Wei Liou, Jacob T. Barlow, Tzu-Ting Lai, Gil Sharon, Catherine E. Schretter, Brittany D. Needham, Madelyn I. Wang, Weiyi Tang, James Ousey, Yuan-Yuan Lin, Tzu-Hsuan Yao, Reem Abdel-Haq, Keith Beadle, Viviana Gradinaru, Rustem F. Ismagilov, Sarkis K. Mazmanian

Issue&Volume: 2021-06-30

Abstract: Social interactions among animals mediate essential behaviours, including mating, nurturing, and defence1,2. The gut microbiota contribute to social activity in mice3,4, but the gut–brain connections that regulate this complex behaviour and its underlying neural basis are unclear5,6. Here we show that the microbiome modulates neuronal activity in specific brain regions of male mice to regulate canonical stress responses and social behaviours. Social deviation in germ-free and antibiotic-treated mice is associated with elevated levels of the stress hormone corticosterone, which is primarily produced by activation of the hypothalamus–pituitary–adrenal (HPA) axis. Adrenalectomy, antagonism of glucocorticoid receptors, or pharmacological inhibition of corticosterone synthesis effectively corrects social deficits following microbiome depletion. Genetic ablation of glucocorticoid receptors in specific brain regions or chemogenetic inactivation of neurons in the paraventricular nucleus of the hypothalamus that produce corticotrophin-releasing hormone (CRH) reverse social impairments in antibiotic-treated mice. Conversely, specific activation of CRH-expressing neurons in the paraventricular nucleus induces social deficits in mice with a normal microbiome. Via microbiome profiling and in vivo selection, we identify a bacterial species, Enterococcus faecalis, that promotes social activity and reduces corticosterone levels in mice following social stress. These studies suggest that specific gut bacteria can restrain the activation of the HPA axis, and show that the microbiome can affect social behaviours through discrete neuronal circuits that mediate stress responses in the brain.

DOI: 10.1038/s41586-021-03669-y

Source: https://www.nature.com/articles/s41586-021-03669-y

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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