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Suppression of Microglial Activation by Acute Ethanol Administration through HT7 Stimulation

급성 알코올 투여 백서의 신문혈 자극이 소교세포 활성에 미치는 영향

  • Su Yeon Seo (Oriental Medicine Research Department, Korea Institute of Oriental Medicine (KIOM)) ;
  • Se Kyun Bang (Oriental Medicine Research Department, Korea Institute of Oriental Medicine (KIOM)) ;
  • Suk Yun Kang (Oriental Medicine Research Department, Korea Institute of Oriental Medicine (KIOM)) ;
  • Seong Jin Cho (Oriental Medicine Research Department, Korea Institute of Oriental Medicine (KIOM)) ;
  • Kwang-Ho Choi (Oriental Medicine Research Department, Korea Institute of Oriental Medicine (KIOM)) ;
  • Yeonhee Ryu (Oriental Medicine Research Department, Korea Institute of Oriental Medicine (KIOM))
  • 서수연 (한국한의학연구원 한의과학연구부) ;
  • 방세권 (한국한의학연구원 한의과학연구부) ;
  • 강석윤 (한국한의학연구원 한의과학연구부) ;
  • 조성진 (한국한의학연구원 한의과학연구부) ;
  • 최광호 (한국한의학연구원 한의과학연구부) ;
  • 류연희 (한국한의학연구원 한의과학연구부)
  • Received : 2024.04.19
  • Accepted : 2024.06.04
  • Published : 2024.06.27

Abstract

Objectives : The sigma-1 receptor is implicated in stress, depression, psychostimulant sensitization, and addiction vulnerability. Prior studies have indicated that ethanol exposure modulates sigma-1 receptor activity within the Ventral Tegmental Area (VTA). Here, we explore the sub-mechanisms underlying sigma-1 receptor activity induced by HT7 (Shinmun) stimulation in behavioral alterations following acute ethanol (ETOH) administration. Methods : Male Wistar rats were investigated for pro- and anti-inflammatory markers after injection of ETOH (1 g/kg) using cytokine enzyme-linked immunosorbent assay (ELISA)s. After confirming that HT7 stimulation changed the total distance traveled in the open field test (OFT), protein changes in the Ventral tegmental area (VTA) were measured by Western blotting. The expression level of inducible nitric oxide synthase (iNOS) after administration of a sigma-1 receptor antagonist (dihydrobromide 1047; BD1047, 10 mg/kg i.p.) and Shenmen (HT7) stimulation was compared. Results : As a result, acute ETOH administration increased proinflammatory marker levels (TNF-𝛼 and IL-6). HT7 stimulation restored the total distance response after acute ethanol administration. In addition, in the VTA, the levels of a microglial marker (iNOS), sigma-1 receptor and protein kinase C, which are predicted to be involved in up- and downregulation, were restored by HT7 stimulation. In particular, HT7 stimulation modulates iNOS expression through effects similar to BD treatment. This study suggests that the stimulatory effect of HT7 may be driven by microglial activation. Conclusions : Microglial activity is regulated by sigma-1 receptor, and sigma-1 receptor activity is regulated by HT7 stimulation. Significantly, we demonstrate that HT7 stimulation ameliorates behavioral alterations induced by acute ETOH administration through microglial activation within the VTA.

Keywords

Acknowledgement

This work was supported a grant from the Korea Institute of Oriental Medicine, Korea (No. KSN2022210) and supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (No. 2021R1A2C1093712).

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