PMID- 28615695 OWN - NLM STAT- MEDLINE DCOM- 20190513 LR - 20240326 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 IP - 1 DP - 2017 Jun 14 TI - Brain-derived neurotrophic factor is regulated via MyD88/NF-kappaB signaling in experimental Streptococcus pneumoniae meningitis. PG - 3545 LID - 10.1038/s41598-017-03861-z [doi] LID - 3545 AB - Streptococcus pneumoniae meningitis is an intractable disease of the central nervous system (CNS). Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophic family and found to participate in the immune inflammatory response. In this study, we investigated if activation of the classical inflammatory signaling pathway, myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-kappaB), regulates BDNF expression in experimental S. pneumoniae meningitis. MyD88 knockout (myd88-/-) mice and wild-type littermates were infected intracisternally with S. pneumoniae suspension. Twenty-four hours after inoculation, histopathology of brains was evaluated. Cytokine and chemokine in brains and spleens was analyzed using ELISA. NF-kappaB activation was evaluated using EMSA. Cortical and hippocampal BDNF was assessed using RT-PCR and ELISA, respectively. BDNF promoter activity was evaluated using ChIP-PCR. myd88-/- mice showed an obviously weakened inflammatory host response. This diminished inflammation was consistent with worse clinical parameters, neuron injury, and apoptosis. Deficiency in MyD88 was associated with decreased BDNF expression. Furthermore, we identified a valid kappaB-binding site in the BDNF promoter, consistent with activation of NF-kappaB induced by inflammation. To sum up, MyD88/NF-kappaB signaling has a crucial role in up-regulating BDNF, which might provide potential therapeutic targets for S. pneumoniae meningitis. FAU - Xu, Danfeng AU - Xu D AD - Department of Pediatric Neurology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, P.R. China. FAU - Lian, Di AU - Lian D AD - Department of Pediatric Neurology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, P.R. China. FAU - Zhang, Zhijie AU - Zhang Z AD - Department of Pediatric Neurology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, P.R. China. FAU - Liu, Ying AU - Liu Y AD - Department of Clinical Laboratory, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, P.R. China. FAU - Sun, Jiaming AU - Sun J AD - Department of Pathology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, P.R. China. FAU - Li, Ling AU - Li L AD - Department of Pediatric Neurology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, P.R. China. linglidoctor@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170614 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Bdnf protein, mouse) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NF-kappa B p50 Subunit) RN - 147257-52-1 (Nfkb1 protein, mouse) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*biosynthesis MH - Disease Models, Animal MH - *Gene Expression Regulation MH - Meningitis, Pneumococcal/*pathology MH - Mice MH - Mice, Knockout MH - Myeloid Differentiation Factor 88/deficiency/*metabolism MH - NF-kappa B p50 Subunit/*metabolism MH - *Signal Transduction PMC - PMC5471242 COIS- The authors declare that they have no competing interests. EDAT- 2017/06/16 06:00 MHDA- 2019/05/14 06:00 PMCR- 2017/06/14 CRDT- 2017/06/16 06:00 PHST- 2017/02/03 00:00 [received] PHST- 2017/05/04 00:00 [accepted] PHST- 2017/06/16 06:00 [entrez] PHST- 2017/06/16 06:00 [pubmed] PHST- 2019/05/14 06:00 [medline] PHST- 2017/06/14 00:00 [pmc-release] AID - 10.1038/s41598-017-03861-z [pii] AID - 3861 [pii] AID - 10.1038/s41598-017-03861-z [doi] PST - epublish SO - Sci Rep. 2017 Jun 14;7(1):3545. doi: 10.1038/s41598-017-03861-z.