Kwon Oh Wook, Hwang Park Youngja, Kim Dalnim, Kwon Hyog Young, Yang Hyun-Jeong
Department of Integrative Biosciences, University of Brain Education, Cheonan, Republic of Korea.
Metabolomics Laboratory, College of Pharmacy, Korea University, Sejong, Republic of Korea.
J Ginseng Res. 2024 Sep;48(5):481-493. doi: 10.1016/j.jgr.2024.03.005. Epub 2024 Mar 25.
Post-weaning social isolation (SI) reduces sociability, gene expressions including myelin genes in the medial prefrontal cortex (mPFC), and alters microbiome compositions in rodent models. Korean Red Ginseng (KRG) and its major ginsenoside Rb1 have been reported to affect myelin formation and gut metabolites. However, their effects under post-weaning SI have not been investigated. This study investigated the effects of KRG and Rb1 on sociability, gene expressions in the mPFC, and gut metabolites under post-weaning SI.
C57BL/6J mice were administered with water or KRG (150, 400 mg/kg) or Rb1 (0.1 mg/kg) under SI or regular environment (RE) for 2 weeks during the post-weaning period (P21-P35). After this period, mice underwent a sociability test, and then brains and ceca were collected for qPCR/immunohistochemistry and non-targeted metabolomics, respectively.
SI reduced sociability compared to RE; however, KRG (400 mg/kg) and Rb1 significantly restored sociability under SI. In the mPFC, expressions of genes related to myelin, neurotransmitter, and oxidative stress were significantly reduced in mice under SI compared to RE conditions. Under SI, KRG and Rb1 recovered the altered expressions of several genes in the mPFC. In gut metabolomics, 313 metabolites were identified as significant among 3027 detected metabolites. Among the significantly changed metabolites in SI, some were recovered by KRG or Rb1, including metabolites related to stress axis, inflammation, and DNA damage.
Altered sociability, gene expression levels in the mPFC, and gut metabolites induced by two weeks of post-weaning SI were at least partially recovered by KRG and Rb1.
断奶后社会隔离（SI）会降低社交能力，改变包括内侧前额叶皮质（mPFC）中髓磷脂基因在内的基因表达，并改变啮齿动物模型中的微生物群组成。据报道，韩国红参（KRG）及其主要人参皂苷Rb1会影响髓磷脂形成和肠道代谢产物。然而，它们在断奶后SI条件下的作用尚未得到研究。本研究调查了KRG和Rb1对断奶后SI条件下社交能力、mPFC中的基因表达以及肠道代谢产物的影响。
在断奶期（P21 - P35）的2周内，将C57BL/6J小鼠在SI或正常环境（RE）下给予水或KRG（150、400 mg/kg）或Rb1（0.1 mg/kg）。在此期间过后，对小鼠进行社交能力测试，然后分别收集大脑和盲肠用于qPCR/免疫组织化学和非靶向代谢组学分析。
与RE相比，SI降低了社交能力；然而，KRG（400 mg/kg）和Rb1在SI条件下显著恢复了社交能力。在mPFC中，与髓磷脂、神经递质和氧化应激相关的基因表达在SI条件下的小鼠中与RE条件相比显著降低。在SI条件下，KRG和Rb1恢复了mPFC中几个基因的改变表达。在肠道代谢组学中，在检测到的3027种代谢产物中，有313种被鉴定为显著代谢产物。在SI中显著变化的代谢产物中，一些被KRG或Rb1恢复，包括与应激轴、炎症和DNA损伤相关的代谢产物。
断奶后2周的SI诱导的社交能力改变、mPFC中的基因表达水平以及肠道代谢产物至少部分被KRG和Rb1恢复。
