Hosoi Toru, Yamawaki Yosuke, Kimura Hitomi, Honda Shoko, Ozawa Koichiro
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Yamaguchi, Japan.
Department of Cellular and Molecular Pharmacology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Front Neurosci. 2021 Mar 12;15:621446. doi: 10.3389/fnins.2021.621446. eCollection 2021.
Myeloid differentiation primary response 88 (MyD88) is an adapter protein of the toll-like receptor (TLR) family that regulates innate immune function. Here, we identified a novel role of MyD88 in regulating stress response. MyD88 deficiency decreased immobility time in the forced swim test without affecting locomotor activity in mice. Immobilization stress-induced production of serum corticosterone was also completely inhibited by MyD88 deficiency. Stress induced decrease in glucocorticoid receptor in the hippocampus. On the other hand, stress exposure in MyD88 deficient mice did not cause decrease in its level in the hippocampus. Furthermore, immobilization stress-induced reduction of brain-derived neurotrophic factor (BDNF) levels in the hippocampus was ameliorated by MyD88 deficiency. These results suggest that MyD88 deficiency attenuates depression-like behavior by regulating corticosterone and BDNF levels. Overall, these results indicate the key role of MyD88 in regulating stress response in mice.
髓样分化初级反应88（MyD88）是Toll样受体（TLR）家族的一种衔接蛋白，可调节先天免疫功能。在此，我们确定了MyD88在调节应激反应中的新作用。MyD88缺陷减少了强迫游泳试验中的不动时间，而不影响小鼠的运动活性。MyD88缺陷也完全抑制了固定应激诱导的血清皮质酮产生。应激诱导海马中糖皮质激素受体减少。另一方面，MyD88缺陷小鼠的应激暴露并未导致其海马中该水平下降。此外，MyD88缺陷改善了固定应激诱导的海马中脑源性神经营养因子（BDNF）水平降低。这些结果表明，MyD88缺陷通过调节皮质酮和BDNF水平减轻抑郁样行为。总体而言，这些结果表明MyD88在调节小鼠应激反应中起关键作用。
