Thioredoxin interacting protein drives astrocytic glucose hypometabolism in corticosterone-induced depressive state.

Brain energetics disturbance is a hypothesized cause of depression. Glucose is the predominant fuel of brain energy metabolism; however, the cell-specific change of glucose metabolism and underlying molecular mechanism in depression remains unclear. In this study, we firstly applied 18 F-FDG PET and observed brain glucose hypometabolism in the prefrontal cortex (PFC) of corticosterone-induced depression of rats. Next, astrocytic glucose hypometabolism was identified in PFC slices in both corticosterone-induced depression of rats and cultured primary astrocytes from newborn rat PFC after stress-level corticosterone (100 nM) stimulation. Furthermore, we found the blockage of glucose uptake and the decrease of plasma membrane (PM) translocation of glucose transporter 1 (GLUT1) in astrocytic glucose hypometabolism under depressive condition. Interestingly, thioredoxin interacting protein (TXNIP), a glucose metabolism sensor and controller, was found to be over-expressed in corticosterone-stimulated astrocytes in vivo and in vitro. High TXNIP level could restrict GLUT1-mediated glucose uptake in primary astrocytes in vitro. Adeno-associated virus vector-mediated astrocytic TXNIP over-expression in rat medial PFC suppressed GLUT1 PM translocation, consequently developed depressive-like behavior. Conversely, TXNIP siRNA facilitated GLUT1 PM translocation to recover glucose hypometabolism in corticosterone-exposed cultured astrocytes. Notably, astrocyte-specific knockdown of TXNIP in medial PFC of rats facilitated astrocytic GLUT1 PM translocation, showing obvious antidepressant activity. These findings provide a new astrocytic energetic perspective in the pathogenesis of depression and, more importantly, provide TXNIP as a promising molecular target for novel depression therapy.

[Sexual Violence Against Women and Their Help-Seeking in Taiwan].

BACKGROUND: Sexual violence is a global health and human rights issue that impacts the physical and mental health of victims and increases healthcare costs. PURPOSE: This research was developed to investigate the prevalence of sexual violence against women in Taiwan and the help-seeking behavior of these women. Based on the findings, suggestions are provided for both government policymakers and frontline medical staffs. METHODS: Data for this study were collected using a face-to-face interview survey conducted with women aged 18 to 74 years nationwide. RESULTS: Of the 1,504 women surveyed, 87 (5.76%) reported having suffered from sexual violence. The one-year prevalence was 1.41%, while the lifetime prevalence was 5.76%. Although sexual violence is known to impact physical and mental health, most victims are reluctant to seek help from formal support systems. CONCLUSIONS: Victims of sexual violence often delay seeking help from medical settings. Although the victims identified in this study endured chronic symptoms and psychological trauma, few had made formal disclosures of intimate partner sexual violence (IPSV) incidents. Frontline medical staffs have the opportunity to play an important role in sexual-violence response if they are made aware of incidents of IPSV / non-IPSV. Thus, to facilitate disclosure, screening for IPSV and non-IPSV should be made standard practice in high-risk medical settings.

Unraveling the potential of Morinda officinalis oligosaccharides as an adjuvant of escitalopram in depression treatment and exploring the underlying mechanisms.

ETHNOPHAMACOLOGICAL RELEVANCE: Morinda officinalis oligosaccharides (MOs) is a mixture of oligosaccharides extracted from the roots of Morinda officinalis (MO). It is approved by Chinese Food and Drug Administration (CFDA) for depression treatment. MOs could improve the antidepressant efficacy of escitalopram in clinic. AIM OF THE STUDY: We aim to explore the antidepressant activity and potential mechanism of the combination usage of MOs and escitalopram on animal model of depression. MATERIALS AND METHODS: Depressive animal model was induced by chronic mild stress (CMS). Behavioral tests were conducted to evaluate the antidepressant efficacy of MOs and escitalopram. Serum neurotransmitter levels were detected by High-performance liquid chromatography (HPLC). Quantitative real-time PCR and Western blotting were applied to assay the hippocampus neurotrophic factors' mRNA and protein levels. Peripheral cytokines levels were measured through Enzyme-Linked Immunosorbent Assay (ELISA). Micorglia polization phenotype was assayed by immunofluorescence and flow cytometry. RESULTS: MOs and escitalopram obviously attenuated depression-like behaviors of CMS mice. Importantly, MOs plus escitalopram exhibited better antidepressant activity on CMS mice than monotherapy. At the same time, MOs combined escitalopram treatment significantly increased hippocampus neurotransmitters and neurotrophic factor levels, stimulated hippocampus neurogenesis and relieved central nervous system (CNS) microglia over-activation of CMS mice. The combination therapy had greater effect on neuroprotection and inflammation attenuation of CMS mice than monotherapy. CONCLUSION: Our results indicates MOs combined escitalopram might produce antidepressant activity through protecting neuron activity, relieving inflammation and modulating microglia polarization process.

Fluoxetine increases astrocytic glucose uptake and glycolysis in corticosterone-induced depression through restricting GR-TXNIP-GLUT1 Pathway.

Antidepressant fluoxetine can affect cerebral glucose metabolism in clinic, but the underlying molecular mechanism remains poorly understood. Here, we examined the effect of fluoxetine on brain regional glucose metabolism in a rat model of depression induced by repeated corticosterone injection, and explored the molecular mechanism. Fluoxetine was found to recover the decrease of 18F-fluorodeoxyglucose (18F-FDG) signal in prefrontal cortex (PFC), and increased 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG, a fluorescent glucose analog) uptake in an astrocyte-specific manner in ex vivo cultured PFC slices from corticosterone-induced depressive rats, which were consistent with its improvement of animal depressive behaviors. Furthermore, fluoxetine restricted nuclear translocation of glucocorticoid receptor (GR) to suppress the transcription of thioredoxin interacting protein (TXNIP). Subsequently, it promoted glucose transporter 1 (GLUT1)-mediated glucose uptake and glycolysis of PFC astrocytes through suppressing TXNIP expression under corticosterone-induced depressive state. More importantly, fluoxetine could improve glucose metabolism of corticosterone-stimulated astrocytes via TXNIP-GLUT1 pathway. These results demonstrated that fluoxetine increased astrocytic glucose uptake and glycolysis in corticosterone-induced depression via restricting GR-TXNIP-GLUT1 pathway. The modulation of astrocytic glucose metabolism by fluoxetine was suggested as a novel mechanism of its antidepressant action.

Pterostilbene Attenuates Fructose-Induced Myocardial Fibrosis by Inhibiting ROS-Driven Pitx2c/miR-15b Pathway.

Excessive fructose consumption induces oxidative stress and myocardial fibrosis. Antioxidant compound pterostilbene has cardioprotective effect in experimental animals. This study is aimed at investigating how fructose drove fibrotic responses via oxidative stress in cardiomyocytes and explored the attenuation mechanisms of pterostilbene. We observed fructose-induced myocardial hypertrophy and fibrosis with ROS overproduction in rats. Paired-like homeodomain 2 (Pitx2c) increase, microRNA-15b (miR-15b) low expression, and p53 phosphorylation (p-p53) upregulation, as well as activation of transforming growth factor-ß1 (TGF-ß1)/drosophila mothers against DPP homolog (Smads) signaling and connective tissue growth factor (CTGF) induction, were also detected in fructose-fed rat hearts and fructose-exposed rat myocardial cell line H9c2 cells. The results from p53 siRNA or TGF-ß1 siRNA transfection showed that TGF-ß1-induced upregulation of CTGF expression and p-p53 activated TGF-ß1/Smads signaling in fructose-exposed H9c2 cells. Of note, Pitx2c negatively modulated miR-15b expression via binding to the upstream of the miR-15b genetic loci by chromatin immunoprecipitation and transfection analysis with pEX1-Pitx2c plasmid and Pitx2c siRNA, respectively. In H9c2 cells pretreated with ROS scavenger N-acetylcysteine, or transfected with miR-15b mimic and inhibitor, fructose-induced cardiac ROS overload could drive Pitx2c-mediated miR-15b low expression, then cause p-p53-activated TGF-ß1/Smads signaling and CTGF induction in myocardial fibrosis. We also found that pterostilbene significantly improved myocardial hypertrophy and fibrosis in fructose-fed rats and fructose-exposed H9c2 cells. Pterostilbene reduced cardiac ROS to block Pitx2c-mediated miR-15b low expression and p-p53-dependent TGF-ß1/Smads signaling activation and CTGF induction in high fructose-induced myocardial fibrosis. These results firstly demonstrated that the ROS-driven Pitx2c/miR-15b pathway was required for p-p53-dependent TGF-ß1/Smads signaling activation in fructose-induced myocardial fibrosis. Pterostilbene protected against high fructose-induced myocardial fibrosis through the inhibition of Pitx2c/miR-15b pathway to suppress p-p53-activated TGF-ß1/Smads signaling, warranting the consideration of Pitx2c/miR-15b pathway as a therapeutic target in myocardial fibrosis.

Chaihu-shugan san inhibits inflammatory response to improve insulin signaling in liver and prefrontal cortex of CUMS rats with glucose intolerance.

Depression is a mental illness comorbid risk factor for glucose intolerance worldwide. Chaihu-shugan san, a 'Shu-Gan' formula in traditional Chinese medicine, is clinically used in the treatment of depression. The aim of this study was to investigate whether Chaihu-shugan san improved glucose tolerance with its antidepressant activity in rat model of depression and explore the mechanisms underlying its action on liver-brain inflammation axis. After 6 weeks of chronic unpredictable mild stress (CUMS) procedure, male Wistar rats were given Chaihu-shugan san water extract (925 and 1850 mg/kg) by gavage for the next 6 consecutive weeks. Sucrose consumption test was used to assess animal depressive-like behaviors. Oral glucose tolerance test (OGTT) was employed to define the status of glucose tolerance in rats. Serum alanine aminotransferase (ALT) and interleukin-1 beta (IL-1ß) were measured by commercial kits, respectively. Western blot was used to detect the expression of key proteins in inflammatory signaling cascades including toll-like receptor 4 (TLR4), myeloid differentiation protein 88 (MyD88), nuclear factor-kappa B (NF-κB), Nod-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), cysteinyl aspartate specific proteinase-1 (Caspase-1) and IL-1ß, as well as insulin signaling in liver and prefrontal cortex of rats. Immunohistochemical staining or immunofluorescence staining of NF-κB, and nuclear/cytoplasmic ratio of NF-κB by Western blot were used to describe its nuclear entry in liver and prefrontal cortex of rats. RT-qPCR and Western blot analysis, as well as microRNA-155 (miR-155) mimic or inhibitor transfection were used to explore possible association of MyD88 and miR-155. In this study, Chaihu-shugan san increased sucrose consumption and reduced serum glucose levels in CUMS rats, showing its antidepressant activity with glucose tolerance improvement. Chaihu-shugan san reduced serum levels of ALT and IL-1ß in this animal model. Furthermore, this formula inhibited hepatic and prefrontal cortical inflammatory response by suppressing TLR4/MyD88/NF-κB pathway and NLRP3 inflammasome activation, and improved insulin signaling in CUMS rats. More importantly, Chaihu-shugan san up-regulated miR-155 expression in liver and prefrontal cortex of CUMS rats. These results provide direct evidence that Chaihushugan San can ameliorate depressive-like behaviors by inhibiting liver-brain inflammation axis.

Mental health literacy, stigma and perception of causation of mental illness among Chinese people in Taiwan.

BACKGROUND: Few studies have been performed to explore mental health literacy and stigmatising attitudes towards mental illness and their relationships with causal beliefs about mental illness among Chinese people in Taiwan. AIMS: Using a comparative approach, this study attempted to compare the mental health literacy and stigmatising attitudes of Taiwanese Chinese with those found among Australian and Japanese participants in other studies and to explore how mental health literacy and stigmatising attitudes relate to different perceptions of causes of mental illness. METHODS: A convenience sample of 287 participants completed a battery of standardised questionnaires. RESULTS: A much lower percentage of Taiwanese people than Australians could correctly identify depression and schizophrenia. The Taiwanese respondents rated psychiatrists and clinical psychologists as more helpful than social workers and general practitioners (GPs) and expressed more uncertainty about the usefulness of certain medications when compared to the Australian and Japanese samples. Interestingly, Taiwanese Chinese hold similarly high levels of stigma towards schizophrenia, but lower levels of stigma towards depression when compared to the Japanese respondents. Taiwanese respondents who have higher levels of mental health literacy about schizophrenia were less willing to interact with people with schizophrenia than those with lower levels of mental health literacy. CONCLUSION: This study underlines the need for public education programmes to improve knowledge of various mental illnesses and to reduce stigmatising attitudes among Taiwanese Chinese. The aforementioned socially and culturally driven beliefs must be taken into consideration so that culturally relevant education programmes can be developed.

Comparing the mental health literacy of Chinese people in Australia, China, Hong Kong and Taiwan: Implications for mental health promotion.

Using data of 200, 522, 572, and 287 Chinese from Australia, China, Hong Kong and Taiwan respectively, this study aimed at comparing the mental health literacy of Chinese people from different communities, and between Chinese communities and the Australian general public. The participants were asked questions that assessed their recognition of depression and schizophrenia. Compared with the Australians, much lower percentages of Chinese in the four Chinese communities could correctly identify depression and early schizophrenia. Commonalities in the preference for 'psychiatrist', 'psychologist', 'Chinese medical doctor', and 'Chinese traditional healer', a lack of knowledge of medications, and a higher likelihood of endorsement of traditional Chinese medicines were found among the four Chinese communities. Differences in the preference for 'general practitioner' and 'social worker', and a higher percentage of endorsement of herbal medicines were observed among the different Chinese communities. Cultural factors such as Chinese perceptions of mental illness, and socio-contextual factors such as differences in mental health care system in the four communities were offered to explain these commonalities and differences. Mental health promotion programmes for Chinese people may need to consider the above-mentioned cultural and socio-contextual factors so that specific promotion programmes can be developed.

Prevalence of sexual abuse of people with intellectual disabilities in Taiwan.

Although sexual abuse of people with intellectual disabilities has emerged as a major issue in the West over recent years, few researchers have examined this issue in Taiwan. The prevalence and current state of sexual abuse for people with intellectual disabilities in Taiwan were investigated here. Results of face-to-face interviews with 336 subjects revealed that the prevalence of sexual abuse for this population is 5.4%. This low prevalence of sexual abuse has certain cultural implications; most people with intellectual disabilities live in supported living settings and are, therefore, excluded from community life. Increased effort is needed to develop effective service programs for abuse prevention and strategies should be developed to improve the limitations in the present study.