STAT3 activation and c-FOS expression in the brain following peripheral administration of bacterial DNA

Abstract

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 immunotistochemisty 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.