Estrogen receptor‐β of microglia underlies sexual differentiation of neuronal protection via ginsenosides in mice brain

Summary 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 meni...

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Bibliographic Details
Published in:CNS neuroscience & therapeutics 2018-10, Vol.24 (10), p.930-939
Main Authors: Lee, Seungyeop, Lee, Si‐On, Kim, Gyu‐Lee, Rhee, Dong‐Kwon
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Apoptosis - drug effects
Bacteria
Bacterial infections
bacterial meningitis
Brain Injuries - etiology
Brain Injuries - pathology
Brain Injuries - prevention & control
Brain injury
Brain-derived neurotrophic factor
Cell Line, Transformed
Disease Models, Animal
Estrogen Receptor beta - genetics
Estrogen Receptor beta - metabolism
Estrogen receptors
estrogen receptor‐β
Female
Gene Expression Regulation - drug effects
Ginseng
ginsenoside Rb1, Rg3
Ginsenosides
Ginsenosides - therapeutic use
Immune clearance
Immune response
Inflammation
Janus kinase 2
Male
Meningitis
Mice
Mice, Inbred C57BL
Microglia
Microglia - drug effects
Microglia - metabolism
neuroinflammation
Neuroprotective Agents - therapeutic use
Original
Phosphorylation
Pneumococcal Infections - complications
Pneumococcal Infections - drug therapy
Proto-Oncogene Proteins c-bcl-2 - metabolism
RNA, Small Interfering - genetics
RNA, Small Interfering - metabolism
Sex Characteristics
Sex differentiation
Stat5 protein
Streptococcus infections
Streptococcus pneumoniae
Therapeutic applications
Time Factors
Traumatic brain injury
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Summary:Summary 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‐β (ER‐β) 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.
ISSN:1755-5930
1755-5949
DOI:10.1111/cns.12842