Moesin-like gene 1 antisense was increased in the postmortem cortex of patients with autism spectrum disorders. Overexpression of moesin-like gene 1 antisense induces downregulation of moesin expression in cortical neurons, resulting in decreased neurite numbers and length. However, moesin knockout (KO) mice have not been reported about behavioral abnormalities or delayed brain development, indicating autism spectrum disorders. Here, we generated moesin KO mice by using the CRISPR/CAS9 system and observed their behaviors. Moesin KO mice exhibited abnormal developmental behaviors at 7 days, cognitive decline in the passive avoidance and Y maze tests, and anxiety symptoms in the open field test compared to wild-type mice at 3 months. Moreover, the primary cortical neurons of moesin KO mice showed a low cell survival rate and low expression of proteins involved in neuronal development and growth, such as MAP2, DCX, SOX2, SNAP25, and PSD95. Western blot analysis also revealed the downregulation of various synaptic proteins, such as syntaxin 1A and CDK5, in the brain of moesin KO adult mice. Moreover, the phosphorylation levels of synapsin I, MUNC18, ERK, and CREB were downregulated in the brains of moesin-KO mice. Furthermore, risperidone reversed the impaired memory function and synapsin I and ERK phosphorylation in the cortical tissue of moesin-KO mice. Thus, these results suggest that moesin affects neurodevelopmental and cognitive processes, plays an important role in the synaptic plasticity showing normal synapse structure and function, and that risperidone can reverse these synaptopathy and neurodevelopmental disorders.

Background: BaelanChagsangBang (BCB), a herbal formulation consisting of eleven herbs, may be prescribed as a reproductive functional supplement to improve ovulation and implantation during the treatment of infertility and recurrent abortion in Korean Medicine. This study aimed to investigate the effects and action mechanisms of water-extracted BCB on endometrial receptivity and blastocyst implantation under normal conditions and in a mifepristone (RU486)-induced implantation failure murine model.Methods: In vitro, the antioxidant potentials of BCB were evaluated using DPPH and superoxide anion radical scavenging assays and a DCFH-DA assay, and the cytotoxic and cytoprotective effects of BCB were confirmed using an MTT assay. In vivo, C57BL/6 female mice (n = 6 per group) orally received BCB (300 mg/kg/day), a dose similar to that used clinically, from 7 days before pregnancy until the end of the experiment. On day 4 of pregnancy, RU486 (4 mg/kg) was injected subcutaneously to induce implantation failure. The effect of BCB on embryo implantation was evaluated by implantation rate analysis, histological examination, and western blotting of uterus tissues.Results: BCB water extract showed strong anti-oxidative and cytoprotective effects in vitro. In vivo administration of BCB water extract increased the number of newborn pups in BCB-treated mice versus sham-treated mice under normal conditions and improved the number of implantation sites in pregnant mice despite RU486 injection. BCB increased the protein levels of cyclooxygenase-2 and inducible nitric oxide synthase through IκB activation. Moreover, the expression levels of matrix metalloproteinases (MMPs) at uterus implantation sites were up-regulated in the BCB-treated group as compared with those in the RU486-treated group. Conclusion: These results show BCB improved embryo implantation through IκB activation in our mouse model and suggest that BCB has therapeutic potential in the context of poor endometrial receptivity.

BackgroundBaelan Chagsang Bang (BCB), consisting of a mixture of 11 herbs, may be prescribed as a reproductive function supplement to improve ovulation and implantation during the treatment of infertility and recurrent abortion in Oriental Medicine. This study aimed to investigate the effects and mechanisms of action of water-extracted BCB on endometrial receptivity and blastocyst implantation in a mifepristone (RU486)-induced implantation failure model.MethodsIn in vitro, antioxidant potentials of BCB were evaluated using DPPH and superoxide anion radical scavenging assays and DCFH-DA assay. In vivo, C57BL/6 female mice (n = 6 per group) orally received BCB (300 mg/kg/day), a dose similar to that used clinically. BCB was administrated from 7 days before pregnancy until the end of the experiment. They were housed with male mice until pregnancy was confirmed. On day 4 of pregnancy, RU486 (4 mg/kg) was injected subcutaneously to induce implantation failure.ResultsAdministration of the BCB water extract increased the number of newborn pups in BCB-treated mice compared to that of sham-treated mice and improved the number of implantation sites in pregnant mice despite RU486 injection. BCB increased the protein expression level of cyclooxygenase-2 and inducible nitric oxide synthase through IκB activation. Moreover, the expression level of matrix metalloproteinases (MMPs) at the uterus implantation site was up-regulated in the BCB-treated group compared to that of the RU486-treated group. To determine the mechanisms of action of BCB, the anti-oxidative effect of BCB was examined via in vitro assay. The BCB water extract showed strong anti-oxidative effects in the DPPH assay and the superoxide anion free-radical scavenging activity assay.ConclusionOur findings provide evidence that BCB has therapeutic potential against poor endometrial receptivity.