Targeting the succinate receptor effectively inhibits periodontitis.

Periodontal disease (PD) is one of the most common inflammatory diseases in humans and is initiated by an oral microbial dysbiosis that stimulates inflammation and bone loss. Here, we report an abnormal elevation of succinate in the subgingival plaque of subjects with severe PD. Succinate activates succinate receptor-1 (SUCNR1) and stimulates inflammation. We detected SUCNR1 expression in the human and mouse periodontium and hypothesize that succinate activates SUCNR1 to accelerate periodontitis through the inflammatory response. Administration of exogenous succinate enhanced periodontal disease, whereas SUCNR1 knockout mice were protected from inflammation, oral dysbiosis, and subsequent periodontal bone loss in two different models of periodontitis. Therapeutic studies demonstrated that a SUCNR1 antagonist inhibited inflammatory events and osteoclastogenesis in vitro and reduced periodontal bone loss in vivo. Our study reveals succinate's effect on periodontitis pathogenesis and provides a topical treatment for this disease.

Mere Exposure Effect Is Sometimes Insensitive to Mood Inductions.

The mere exposure effect (MEE) is defined as repeated exposures to a stimulus enhancing affective evaluations of that stimulus (Zajonc, 1968). The three prominent explanations of the MEE are Zajonc's "neophobia" account, the uncertainty reduction account, and the perceptual fluency approach. Zajonc's "neophobia" account posits that people have an inherent low level of fear of novel objects and exposure to the objects partially extinguishes this novelty-based fear. The uncertainty reduction account asserts that people find uncertainty aversive and habituation reduces uncertainty. The fluency account postulates that people "like" representations of things with which they are fluent. In four experiments, we induced positive and negative moods before or after target exposures. In addition to assessing the MEE in each condition, we assessed the mood induction. The central hypothesis assessed in this series was that there would be an interaction between mood and the MEE. Although the three accounts of the MEE generated divergent predictions, none of the accounts were well supported by the data. Tests for mood induction demonstrated the efficacy of the induction procedures and the MEE was consistently observed, but Bayesian analysis indicated that at least in the present preparation mood had no effect on the MEE.