Reversible photocontrol of dopaminergic transmission in wild-type animals

Understanding the dopaminergic system is a priority in neurobiology and neuropharmacology. Dopamine receptors are involved in the modulation of fundamental physiological functions and dysregulation of dopaminergic transmission is associated with major neurological disorders. However, the available tools to dissect the endogenous dopaminergic circuits have limited specificity, reversibility, resolution, or require genetic manipulation. Here we introduce azodopa, a novel photoswitchable ligand that enables reversible spatiotemporal control of dopaminergic transmission. We demonstrate that azodopa activates D1-like receptors in vitro in a light-dependent manner. Moreover, it enables reversibly photocontrolling zebrafish motility on a time scale of seconds and allows separating the retinal component of dopaminergic neurotransmission. Azodopa increases the overall neural activity in the cortex of anesthetized mice and displays illuminationdependent activity in individual cells. Azodopa is the first photoswitchable dopamine agonist with demonstrated efficacy in wildtype animals and opens the way to remotely controlling dopaminergic neurotransmission for fundamental and therapeutic purposes

Comparative Study of Microbial-Derived Phenolic Metabolites in Human Feces after Intake of Gin, Red Wine, and Dealcoholized Red Wine

The analysis of microbial phenolic metabolites in fecal samples from in vivo studies is crucial to understanding the potential modulatory effects derived from polyphenol consumption and its overall health effects, particularly at the gut level. In this study, the composition of microbial phenolic metabolites in human feces collected after regular consumption of either red wine, dealcoholized red wine, or gin was analyzed by UPLC-ESI-MS/MS. Red wine interventions produce a change in the content of eight phenolic acids, which are probably derived from the catabolism of flavan-3-ols and anthocyanins, the main flavonoids in red wine. Moreover, alcohol seemed not to influence the formation of phenolic metabolites by the gut microbiota. A principal component analysis revealed large interindividual differences in the formation of microbial metabolites after each red wine polyphenol intervention, but not after the gin intervention, indicating differences in the gut microbial composition among subjects