Role of allopregnanolone-mediated γ-aminobutyric acid A receptor sensitivity in the pathogenesis of premenstrual dysphoric disorder: Toward precise targets for translational medicine and drug development.

Premenstrual dysphoric disorder (PMDD) can be conceptualized as a disorder of suboptimal sensitivity to neuroactive steroid hormones. Its core symptoms (emotional instability, irritability, depression, and anxiety) are related to the increase of stress sensitivity due to the fluctuation of hormone level in luteal phase of the menstrual cycle. In this review, we describe the emotional regulatory effect of allopregnanolone (ALLO), and summarize the relationship between ALLO and γ-aminobutyric acid A (GABAA) receptor subunits based on rodent experiments and clinical observations. A rapid decrease in ALLO reduces the sensitivity of GABAA receptor, and reduces the chloride influx, hindered the inhibitory effect of GABAergic neurons on pyramidal neurons, and then increased the excitability of pyramidal neurons, resulting in PMDD-like behavior. Finally, we discuss in depth the treatment of PMDD with targeted GABAA receptors, hoping to find a precise target for drug development and subsequent clinical application. In conclusion, PMDD pathophysiology is rooted in GABAA receptor sensitivity changes caused by rapid changes in ALLO levels. Targeting GABAA receptors may alleviate the occurrence of PMDD.

Synthesis and characterization of tannic acid-PEG hydrogel via Mitsunobu polymerization.

Tannic acid (TA) based materials have received significant interest owing to their broad spectrum of chemical and biological properties. Herein, a novel tannic acid based hydrogel, TA-PEG hydrogel, was synthesized via Mitsunobu polymerization/polycondensation, in which TA and polyethylene glycol (PEG) were simply crosslinked together by ether linkages. This method was performed in one pot, straightforward, metal free and robust, ignoring the strong ionic/hydrophobic interactions between tannic acid and PEG. Bearing catechol and pyrogallol units from TA, TA-PEG hydrogel did not only reduce the silver and gold precursor, but also served as a capping agent and stabilizer for the in situ formed Au and Ag nanoparticles (NPs). Furthermore, the antioxidant activity of the hydrogel was excellent (94%) in the case of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging. TA-PEG hydrogel also showed antibacterial activity against Staphylococcus aureus and Escherichia coli. This work suggested a new method leading to polyphenol based soft materials rather than a complex coacervated microstructure. The resulting TA-PEG hydrogel has potential application in biomedical materials.