RESUMO
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.
RESUMO
<p><b>OBJECTIVE</b>To study the therapeutic effect of traditional Chinese herbal medicinal preparation Tangshenqing (TSQ) combined with alprostadil in the treatment of early- and intermediate-stage diabetic nephropathy (DN).</p><p><b>METHODS</b>One hundred and twenty DN patients were randomized into 3 groups for different treatment protocols. The patients in the control group were given the basic treatment (low-protein diabetic diet and rigorous control of blood glucose, blood pressure, and blood fatty acid), and those in treatment group A received TSQ (containing Astragalus membranaceus, Panax notoginseng, Epimedium brevicornum, etc) in addition to the basic treatment, and those in treatment group B were treated with alprostadil injections (for 14 consecutive days) in addition to the treatment given in group A. Therapeutic effect evaluation was carried out after a 30-day treatment in all the patients.</p><p><b>RESULTS</b>The overall efficaey rate of the treatment was 78.37% in the control group, 88.57% in the treatment group A, and 94.44% in treatment group B, suggesting better therapeutic effect in the latter two groups than in the control group (P<0.05). Patients in all the 3 groups exhibited symptomatic improvement of various degrees, but the treatment group B had the best results. After the treatments, the patients' blood glucose and fatty acids were lowered, without obvious difference between the 3 groups. Compared with the control group, the patients in the two treatment groups showed significant reduction in fibrinogen, 24-h urine microprotein and urine protein after the treatment (P<0.01 or 0.05).</p><p><b>CONCLUSION</b>Combined use of traditional Chinese herbal medicine TSQ and alprostadil injections produces definite therapeutic effect on early- to intermediate-stage DN.</p>