Atorvastatin ameliorates cognitive impairment, Aß1-42 production and Tau hyperphosphorylation in APP/PS1 transgenic mice.

Amyloid-beta (Aß) interacts with the serine/threonine protein kinase AKT (also known as protein kinase B)/glycogen synthase kinase 3ß (GSK3ß) pathway and deactivates GSK3ß signaling, which result in microtubule protein tau phosphorylation. Atorvastatin, a HMG-CoA reductase inhibitor, has been proven to improve learning and memory performance, reduce Aß and phosphorylated tau levels in mouse model of Alzheimer's disease (AD). However, it still remains unclear whether atorvastatin is responsible for regulation of AKT/GSK3ß signaling and contributes to subsequent down-regulation of Aß1-42 and phosphorylated tau in APP/PS1 transgenic (Tg APP/PS1) mice. Herein, we aimed to investigate the possible impacts of atorvastatin (10 mg/kg, p.o.) on the memory deficit by behavioral tests and changes of AKT/GSK3ß signaling in hippocampus and prefrontal cortex by western blot test in Tg APP/PS1 mice. The results showed that treatment with atorvastatin significantly reversed the memory deficit in the Tg APP/PS1 mice in a novel object recognition and the Morris water maze tests. Moreover, atorvastatin significantly attenuated Aß1-42 accumulation and phosphorylation of tau (Ser396) in the hippocampus and prefrontal cortex of Tg APP/PS1 mice. In addition, atorvastatin treatment also increased phosphorylation of AKT, inhibited GSK3ß activity by increasing phosphorylation of GSK3ß (Ser9) and decreasing the beta-site APP cleaving enzyme 1 (BACE1) expression. These results indicated that the memory ameliorating effect of atorvastatin may be, in part, by regulation the AKT/GSK3ß signaling which may contribute to down-regulation of Aß1-42 and tau hyperphosphorylation.

Influence of parental attitudes and coping styles on mental health during online teaching in the COVID-19 pandemic.

During the COVID-19 pandemic, the online delivery model became the primary mode of education. With multiple pressures on society and families, mental health issues for parents have become particularly pronounced. Most of the current research has focused on the psychological state of education practitioners and children, with little attention to parents' mental health issues. Therefore, this study explored the attitudes and coping styles of parents who experienced the process of their children being taught online over a long period and the factors influencing their mental health. This cross-sectional study was conducted between November 2021 and January 2022, using an anonymous online questionnaire to survey 1500 parents with children aged 6-13 years. The Chinese versions of the Patient Health Questionnaire Depression Scale (PHQ-9), the Parenting Stress Scale (PSS), the General Mental Health Questionnaire (GHQ-12), and the Brief Coping Style Scale (SCSQ), and a related factors questionnaire were used to survey the subjects. The normal distribution of the data was examined using the Shapiro-Wilk method. A multivariate regression analysis was conducted to identify factors significantly associated with parental mental health during the COVID-19 pandemic. Only 30.24% of parents agreed with online classes during the pandemic, and 52.28% used positive coping methods during stressful situations. Multivariate regression models identified significant factors associated with parental mental health: parent's gender, child's grade level, perceived stress about online classes, whether the child has ADHD, positive or negative coping styles, and subjective attitudes of support for online classes or not. The results of the study suggest that as online classes become more socially acceptable, it is necessary to be concerned about the risk of mental illness for parents and develop policies and interventions, especially for parents who adopt negative coping styles and endorse online classes. The focus should be on the stress of online classes on parents, improving the acceptance of online classes and psychological well-being, regulating the way parents deal with their children, and targeting subgroups of children with ADHD symptoms during the COVID-19 pandemic.

Major depressive disorder is correlated with the mitochondrial ND1 T3394C mutation in two Han Chinese families: Two case reports.

BACKGROUND: Major depressive disorder (MDD) is the most frequent reason of disabled people in the world, as reported by the World Health Organization. However, the diagnosis of MDD is mainly based on clinical symptoms. CASE SUMMARY: The clinical, genetic, and molecular characteristics of two Chinese families with MDD are described in this study. There were variable ages of onset and severity in depression among the families. Both Chinese families had a very low pre-valence of MDD. The mitochondrial genomes of these pedigrees were sequenced and indicated a homoplasmic T3394C (Y30H) mutation, with the polymorphism located at a highly conserved tyrosine at position 30 of ND1. The analysis also revealed unique sets of mitochondrial DNA (mtDNA) polymorphisms orig-inating from haplogroups M9a3 and M9a. CONCLUSION: This finding of the T3394C mutation in two unrelated depressed patients provides strong evidence that this mutation may have a part in the etiology of MDD. However, In these two Chinese families having the T3394C mutation, no functional mtDNA mutation was observed. Therefore, T3394C mutations are related with MDD, and the phenotypic manifestation of these mutations may be affected by changes in nuclear genes or environmental factors.

The antidepressant-like effects of biperiden may involve BDNF/TrkB signaling-mediated BICC1 expression in the hippocampus and prefrontal cortex of mice.

Preclinical and clinical studies suggest that neuronal muscarinic acetylcholine receptor (M-AchR) antagonists have antidepressant-like properties. Despite the recent interest in bicaudal C homolog 1 gene (BICC1) as a target for the treatment of depression, the upstream signaling molecules that regulate BICC1 are unknown, and very few studies have addressed the involvement of BICC1 in the antidepressant-like effects of the selective M1-AchR inhibitor, biperiden. Growing evidence indicates that activation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase receptor B (TrkB) signaling may be involved in antidepressant-like activities. In this study, we investigated the role of BDNF/TrkB signaling in the regulation of BICC1 expression in the chronic unpredictable stress (CUS) mouse model of depression. Furthermore, we also examined whether BDNF/TrkB signaling contributes to the antidepressant-like effects of biperiden via down-regulation of BICC1 in the hippocampus and prefrontal cortex of mice. Our current data show that CUS exposure induced significant depression-like behaviors, down-regulation of BDNF/TrkB signaling and up-regulation of BICC1 in the hippocampus and prefrontal cortex of mice. However, biperiden significantly alleviated the CUS-induced abnormalities. Moreover, we found that the effects of biperiden were antagonized by pretreatment with the TrkB antagonist K252a. Our results indicate that BDNF/TrkB signaling may be the major upstream mediator of BICC1 involvement in the antidepressant-like effects of biperiden.

Altered Motor-Striatal Plasticity and Cortical Functioning in Patients with Schizophrenia.

Patients with schizophrenia undergo changes in brain plasticity. In the present study, we characterized motor cortical-striatal plasticity in such patients. Compared with the potentiation following high-frequency repetitive transcranial magnetic stimulation in the control group, the patients demonstrated impaired plasticity of corticostriatal motor-evoked potentials recorded from hand muscles. Notably, the loss of cortical plasticity was correlated with impaired motor learning in a rotary pursuit task. Moreover, the loss of plasticity was correlated with the symptoms of schizophrenia. The results suggest that the progression of schizophrenia is accompanied by altered cortical plasticity and functioning.