A successful antimicrobial therapeutic strategy for the discitis caused by Aggregatibacter actinomycetemcomitans under unknown drug susceptibility: A case report

Aggregatibacter actinomycetemcomitans is well-known as the pathogen of gingivitis or periodontitis, and discitis or vertebral osteomyelitis cases caused by this organism have rarely been reported. Ampicillin or amoxicillin has been used in the previously reported discitis cases; however, no cases have been reported that is treated with levofloxacin. We report the first published case we chose levofloxacin to treat. We failed to perform the susceptibility testing because of the poor growth and fastidious nature of the organism, and the result of susceptibility of amoxicillin was unclear. Levofloxacin, which A. actinomycetemcomitans is usually susceptible to, can be an effective alternative oral antimicrobial agent in such cases.     

Activation of proprotein convertase in the mouse habenula causes depressive-like behaviors through remodeling of extracellular matrix

The lateral habenula (LHb) attracts a growing interest as a regulator of monoaminergic activity which were frequently reported to be defective in depression. Here we found that chronic social defeat stress (CSDS) increased production of pro-inflammatory cytokines in LHb associated with mobilization of monocytes and remodeling of extracellular matrix by increased matrix metalloproteinase (MMP) activity. RNA-seq analysis identified proprotein convertase Pcsk5 as an upstream regulator of MMP activation, with upregulation in LHb neurons of mice with susceptibility to CSDS. PCSK5 facilitated motility of microglia in vitro by converting inactive pro-MMP14 and pro-MMP2 to their active forms, highlighting its role in mobilization of microglia and monocytes in neuroinflammation. Suppression of Pcsk5 expression via small interfering RNA (siRNA) ameliorated depressive-like behaviors and pathological mobilization of monocytes in mice with susceptibility to CSDS. PCSK5-MMPs signaling pathway could be a target for development of the antidepressants targeting the inflammatory response in specific brain regions implicated in depression.Subject terms: Cellular neuroscience, Gene expression analysis