ABSTRACT
Methyl-CpG binding protein 2 (MeCP2) is a basic nuclear protein involved in the regulation of gene expression and microRNA processing. Duplication of MECP2-containing genomic segments causes MECP2 duplication syndrome, a severe neurodevelopmental disorder characterized by intellectual disability, motor dysfunction, heightened anxiety, epilepsy, autistic phenotypes, and early death. Reversal of the abnormal phenotypes in adult mice with MECP2 duplication (MECP2-TG) by normalizing the MeCP2 levels across the whole brain has been demonstrated. However, whether different brain areas or neural circuits contribute to different aspects of the behavioral deficits is still unknown. Here, we found that MECP2-TG mice showed a significant social recognition deficit, and were prone to display aversive-like behaviors, including heightened anxiety-like behaviors and a fear generalization phenotype. In addition, reduced locomotor activity was observed in MECP2-TG mice. However, appetitive behaviors and learning and memory were comparable in MECP2-TG and wild-type mice. Functional magnetic resonance imaging illustrated that the differences between MECP2-TG and wild-type mice were mainly concentrated in brain areas regulating emotion and social behaviors. We used the CRISPR-Cas9 method to restore normal MeCP2 levels in the medial prefrontal cortex (mPFC) and bed nuclei of the stria terminalis (BST) of adult MECP2-TG mice, and found that normalization of MeCP2 levels in the mPFC but not in the BST reversed the social recognition deficit. These data indicate that the mPFC is responsible for the social recognition deficit in the transgenic mice, and provide new insight into potential therapies for MECP2 duplication syndrome.
ABSTRACT
Objective To study the effects of vitamin B_6(VitB_6) injection on small intestinal peristalsis in mice and its mechanisms.Methods The mice were divided into 12 groups:calcium chloride injection group(1 mg/10 g),neostigmine methylsulfate injection group(0.001 5 mg/10 g),atropine sulfate injection group(0.005 mg/10 g),their combination with VitB_6 injection and high/low dose treated groups,high dose VitB_6 injection group(5 mg/10 g),low dose VitB_6 injection group(0.5 mg/10 g) and physiologic saline group(0.1 mL/ 10 g ).After administration 30 minutes,mice were intragastric administration Indian ink(0.1 mL/g),and they were luxated and put to death 20 minutes later.The mice belly were cut open,the length of intestine and distance of Indian ink that had moved were measured,and then the ink progradation rate were calculated.Results Compared with control group,the high dose VitB_6 injection could inhibit normal intestinal peristalsis of mice markedly(P0.05).Conclusions VitB_6 injection can inhibit hyperanakinesia of small intestine in mice,especially high dose.And this will be provided as theory foundation on enterospasm treatment.
ABSTRACT
Objective To explore the effects of extract of Gingko biloba leaves (EGb) on learning, memory and hippoeampal heine oxygenase-1 (HO-1) expression in diabetic rats.Methods The behaviors of streptozotoein-induced diabetic rats were observed by Morris water maze for learning and memory after 6 months of diabetes.The HO-1 mRNA expression and protein expression in hippocampus of diabetic rats were detected by RT- PCR and immunohistochemistry respectively.Results The escape latency time in Morris water maze of diabetic rats was prolonged markedly.HO-1 mRNA and HO-1 protein expressions in hippocampus of diabetic rats were increased (1.635?0.326 vs 0.978?0.214,7.2?1.7 vs 1.9?0.5,respectively,both P＜0.01).The escape latency times in EGb (100,50 mg/kg) treated groups were shortened.HO-1 mRNA and HO-1 protein expressions in hippocampus were decreased at the same time as compared with diabetic group (100 mg/kg:0.954?0.144,2.0?0.8;50 mg/kg:0.988?0.154,2.5?0.6,all P＜0.01).Conclusion EGb can significantly inhibit HO-1 expression in hippocampus and improve learning and memory dysfunction in diabetic rats.