Ultrastructural analysis of social stress-induced neuron-glia interaction underlying neuronal morphological alterations

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15028
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48030:Pharmacology-related
• Research Institution: Kobe University
• Principal Investigator: Nagai Hirotaka 神戸大学, 医学研究科, 助教 (30814587)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ストレス / ミクログリア / シナプス / 三次元電顕 / 膨張顕微鏡法

Outline of Final Research Achievements

Animal studies using various stress models have shown that excessive environmental stress induces brain and peripheral inflammation thereby causing neuronal dysfunction especially in the medial prefrontal cortex (mPFC) and the hippocampus. However, how microglia, a main player in the brain inflammation, interacts with neurons upon stress remains elusive. Here we examined the cell-to-cell interaction of microglia and neurons in the mPFC using three-dimensional electron microscopy and super-resolution microscopy. We subjected male C57BL/6 mice to either single or repeated social defeat stress, and analyzed the brains from those stressed mice or from control mice. We found that social defeat stress increased microglia-neuron interfaces. By the use of expansion microscopy-based super-resolution imaging, we found that the increase in neuron-microglia interaction occurs specifically in the layer II/III but not in the layer I of the mPFC.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

ストレスによる脳機能変化において脳内炎症やミクログリア活性化の意義は確立されてきたものの、神経細胞へ与える影響は不明な部分が多い。本研究はミクログリアと神経細胞が直接的に相互作用することを三次元電子顕微鏡及び超解像イメージングを用いて示し、神経―ミクログリア界面という新たな現象を見出した。今後は本現象を担う分子機序を明らかにすることによってストレス及び精神疾患の新たな創薬標的候補の創出に繋がると考えられる。