STAT3 activation and c-FOS expression in the brain following peripheral administration of bacterial DNA.
To study the role of bacterial DNA in the brain function, we investigated signal transducer and activator of transcription 3 (STAT3) activation and c-FOS expression in the brain by immunohistochemistry in response to peripheral administration of CpG-DNA. CpG-DNA induced phospho-STAT3-immunoreactive cells and c-FOS-positive cells in several brain regions in a different manner. Phospho-STAT3-immunoreactive cells were observed in the circumventricular organs where the blood-brain barrier is weak. On the other hand, CpG-DNA increased c-FOS-positive cells in the paraventricular nucleus of the hypothalamus, and the nucleus of the tractus solitarius (NTS) and the area postrema. Unilateral cervical vagotomy did not modify CpG-DNA-induced c-FOS expression in the NTS, indicating that CpG-DNA-induced activation of the NTS is independent of the afferent vagus nerve input originating from the subdiaphragmatic organs. On the other hand, Toll-like receptor 9 mRNA was expressed in the nodose ganglion. Therefore, it is possible that CpG-DNA activates afferent vagus nerve through the nodose ganglion which subsequently activates the NTS. Present observations represented that peripheral CpG-DNA induced immune event in the brain, and that not only c-FOS but also phosphorylation of STAT3 can be a useful indicator for evaluation of neuro-immune interaction.
Sako
Keisuke
K
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo 060-0812, Japan.
Okuma
Yasunobu
Y
Hosoi
Toru
T
Nomura
Yasuyuki
Y
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D004269:DNA, Bacterial / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry / Q000379:methods; D007274:Injections, Intraperitoneal / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009620:Nodose Ganglion / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050796:STAT3 Transcription Factor; D013997:Time Factors; D051217:Toll-Like Receptor 9; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014628:Vagotomy / Q000379:methods
D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D015534:Trans-Activators