PMID- 29524300 OWN - NLM STAT- MEDLINE DCOM- 20190903 LR - 20210109 IS - 1755-5949 (Electronic) IS - 1755-5930 (Print) IS - 1755-5930 (Linking) VI - 24 IP - 10 DP - 2018 Oct TI - Estrogen receptor-beta of microglia underlies sexual differentiation of neuronal protection via ginsenosides in mice brain. PG - 930-939 LID - 10.1111/cns.12842 [doi] AB - AIMS: Streptococcus pneumoniae infection in acute bacterial meningitis can lead to widespread brain damage and mortality. Inflammatory responses by immune cells in the brain are thought to determine the degree of brain injury. Yet, the mechanisms underlying host responses to pneumococcal meningitis are largely unknown. To explore host responses as a potential therapeutic target for preventing brain injury after pneumococcal meningitis. METHODS: We evaluated signaling mechanisms that minimize neuronal damage caused by pneumococcal infection; specifically, we assessed pathways related to neuronal survival after enhancing estrogen receptor-beta (ER-beta) expression using a natural therapeutic substance known as ginsenoside Rb1 and Rg3 enhanced ginseng. RESULTS: Tissue damage caused by bacterial infection was reduced in Rb1/Rg3-treated mice as a result of microglial activation and the inhibition of apoptosis. Furthermore, Rb1 upregulated the expression of brain-derived neurotrophic factor (BDNF) as well as anti-apoptotic factors including Bcl-2 and Bcl-xL. Using BV2 microglial cells in vitro, Rb1 treatment inhibited microglial apoptosis in a manner associated with JAK2/STAT5 phosphorylation. CONCLUSION: After S. pneumoniae infection in mice, particularly in female mice, Rb1-containing ginseng increased bacterial clearance and survival. These findings inform our understanding of the host immune response to pneumococcal meningitis. CI - (c) 2018 John Wiley & Sons Ltd. FAU - Lee, Seungyeop AU - Lee S AD - School of Pharmacy, Sungkyunkwan University, Suwon, Korea. FAU - Lee, Si-On AU - Lee SO AD - School of Pharmacy, Sungkyunkwan University, Suwon, Korea. FAU - Kim, Gyu-Lee AU - Kim GL AD - School of Pharmacy, Sungkyunkwan University, Suwon, Korea. FAU - Rhee, Dong-Kwon AU - Rhee DK AUID- ORCID: 0000-0003-2792-3254 AD - School of Pharmacy, Sungkyunkwan University, Suwon, Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180309 PL - England TA - CNS Neurosci Ther JT - CNS neuroscience & therapeutics JID - 101473265 RN - 0 (Estrogen Receptor beta) RN - 0 (Ginsenosides) RN - 0 (Neuroprotective Agents) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (RNA, Small Interfering) RN - 7413S0WMH6 (ginsenoside Rb1) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Brain Injuries/etiology/pathology/*prevention & control MH - Cell Line, Transformed MH - Disease Models, Animal MH - Estrogen Receptor beta/genetics/*metabolism MH - Female MH - Gene Expression Regulation/drug effects MH - Ginsenosides/*therapeutic use MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Microglia/drug effects/*metabolism MH - Neuroprotective Agents/*therapeutic use MH - Pneumococcal Infections/complications/drug therapy MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - RNA, Small Interfering/genetics/metabolism MH - *Sex Characteristics MH - Time Factors PMC - PMC6490153 OTO - NOTNLM OT - apoptosis OT - bacterial meningitis OT - estrogen receptor-beta OT - ginsenoside Rb1, Rg3 OT - microglia OT - neuroinflammation COIS- The authors declare no conflict of interests. EDAT- 2018/03/11 06:00 MHDA- 2019/09/04 06:00 PMCR- 2018/03/09 CRDT- 2018/03/11 06:00 PHST- 2018/01/09 00:00 [received] PHST- 2018/02/08 00:00 [revised] PHST- 2018/02/13 00:00 [accepted] PHST- 2018/03/11 06:00 [pubmed] PHST- 2019/09/04 06:00 [medline] PHST- 2018/03/11 06:00 [entrez] PHST- 2018/03/09 00:00 [pmc-release] AID - CNS12842 [pii] AID - 10.1111/cns.12842 [doi] PST - ppublish SO - CNS Neurosci Ther. 2018 Oct;24(10):930-939. doi: 10.1111/cns.12842. Epub 2018 Mar 9.