Effect of cognitive behavioral group therapy on rehabilitation of community patients with schizophrenia: A short-term randomized control trial.

BACKGROUND: The efficacy of cognitive behavioral group therapy (CBGT) for cognitive dys-function and negative symptoms of schizophrenia is established, but more evidence is required. AIM: To assess the effectiveness of CBGT combined with mental health education as a treatment for schizophrenia compared with mental health education alone. METHODS: In all, 120 schizophrenia out-patients were randomized into CBGT combined with mental health education or single mental health education. The primary outcomes were positive and negative symptoms, cognitive function, excitatory factor, anxiety and depression symptom improvements on the positive and negative syndrome scale score. Secondary outcome measures included social function and drug compliance. RESULTS: There were significant differences between CBGT combined with mental health education and single mental health education on measures of positive and negative symptoms, cognitive functions, excitatory factor, anxiety and depression symptoms, and social functions. No other significant difference in outcomes was observed. CONCLUSION: CBGT combined with mental health education may be relevant beneficial treatment method in reducing symptoms, cognitive and social functions of patients with schizophrenia.

Age-related decline in hippocampal tyrosine phosphatase PTPRO is a mechanistic factor in chemotherapy-related cognitive impairment.

Chemotherapy-related cognitive impairment (CRCI) or "chemo brain" is a devastating neurotoxic sequela of cancer-related treatments, especially for the elderly individuals. Here we show that PTPRO, a tyrosine phosphatase, is highly enriched in the hippocampus, and its level is tightly associated with neurocognitive function but declined significantly during aging. To understand the protective role of PTPRO in CRCI, a mouse model was generated by treating Ptpro-/- female mice with doxorubicin (DOX) because Ptpro-/- female mice are more vulnerable to DOX, showing cognitive impairments and neurodegeneration. By analyzing PTPRO substrates that are neurocognition-associated tyrosine kinases, we found that SRC and EPHA4 are highly phosphorylated/activated in the hippocampi of Ptpro-/- female mice, with increased sensitivity to DOX-induced CRCI. On the other hand, restoration of PTPRO in the hippocampal CA3 region significantly ameliorate CRCI in Ptpro-/- female mice. In addition, we found that the plant alkaloid berberine (BBR) is capable of ameliorating CRCI in aged female mice by upregulating hippocampal PTPRO. Mechanistically, BBR upregulates PTPRO by downregulating miR-25-3p, which directly targeted PTPRO. These findings collectively demonstrate the protective role of hippocampal PTPRO against CRCI.

Cation-π Interaction Trigger Supramolecular Hydrogelation of Peptide Amphiphiles.

As an important noncovalent interaction, cation-π interaction plays an essential role in a broad area of biology and chemistry. Despite extensive studies in protein stability and molecular recognition, the utilization of cation-π interaction as a major driving force to construct supramolecular hydrogel remains uncharted. Here, a series of peptide amphiphiles are designed with cation-π interaction pairs that can self-assemble into supramolecular hydrogel under physiological condition. The influence of cation-π interaction is thoroughly investigated on peptide folding propensity, morphology, and rigidity of the resultant hydrogel. Computational and experimental results confirm that cation-π interaction could serve as a major driving force to trigger peptide folding, resultant ß-hairpin peptide self-assembled into fibril-rich hydrogel. Furthermore, the designed peptides exhibit high efficacy on cytosolic protein delivery. As the first case of using cation-π interactions to trigger peptide self-assembly and hydrogelation, this work provides a novel strategy to generate supramolecular biomaterials.

Plasma complement C3 and C3a are increased in major depressive disorder independent of childhood trauma.

BACKGROUND: Dysregulated complement system is linked to pathophysiology of major depressive disorder (MDD). Childhood trauma has been associated with an increased incidence of adult depression via a putative mechanism of immune activation. This study aimed to measure and compare peripheral levels of complement C3, C3a, C1q and C-reactive protein (CRP) in MDD patients and healthy controls and explore the relationship between these molecule levels and childhood trauma history in the participants. METHODS: The participants were 49 medication-free MDD patients and 45 healthy controls. All participants were asked to finish the Childhood Trauma Questionnaire, followed by blood sampling for measurement of plasma complement C3, C3a, C1q and CRP by means of enzyme-linked immunosorbent assay. RESULTS: Peripheral plasma concentration of C3 and C3a in medication-free MDD group was significantly higher than that in the healthy controls; whereas the concentration of plasma C1q and CRP in depressed patients was comparable to that in healthy controls. All these inflammatory factors were not associated to childhood trauma experience in patients with MDD. CONCLUSION: Our data suggest that complement C3 and C3a may be implicated in the pathophysiology of MDD, although traumatic childhood experiences were not associated with the circulating levels of complement C3, C3a, C1q and CRP.

Exposure to multiple metals and the risk of dyslexia - A case control study in Shantou, China.

Environmental heavy metal exposure has been considered to be the risk factor for neurodevelopmental disorders in children. However, the available data on the associations between multiple metals exposure and the risk of dyslexia in China are limited. The purpose of our study was to examine the associations between urinary metal concentrations and Chinese dyslexia risk. A total of 56 Chinese dyslexics and 60 typically developing children were recruited. The urinary concentration of 13 metals were measured by inductively coupled plasma-mass spectrometer (ICP-MS). Binary logistic regression and the Probit extension of Bayesian kernel machine regression (BKMR-P) were used to explore the associations between multiple metal exposure and the risk of Chinese dyslexia. Our results indicated that Co, Zn and Pb were significantly associated with Chinese dyslexia in the multiple-metal exposure model. After adjusting the covariates, a positive association was observed between Pb and the risk of Chinese dyslexia, with the odds ratio (OR) in the highest quartiles of 6.81 (95%CI: 1.07-43.19; p-trend = 0.024). Co and Zn were negatively associated with the risk of Chinese dyslexia. Compared to the lowest quartile, the ORs of Co and Zn in the highest quartile are 0.13 (95%CI: 0.02-0.72; p-trend = 0.026) and 0.18 (95%CI: 0.04-0.88; p-trend = 0.038), respectively. In addition, BKMR-P analysis indicated that with the cumulative level across Co, Zn and Pb increased, the risk of Chinese dyslexia gradually declined and then rebounded, albeit non-significantly, and Pb was the major contributor in this association. In general, the urinary concentrations of Co, Zn and Pb were significantly associated with Chinese dyslexia. More prospective studies are needed to confirm the health effects of multiple metals exposure in children with Chinese dyslexia.

Attachment Insecurity in Rats Subjected to Maternal Separation and Early Weaning: Sex Differences.

Attachment insecurity in the forms of attachment anxiety and avoidance is associated with mental disorders in humans. In this research field, rodents, especially mice and rats, are commonly used to study social behaviors and underlying biological mechanisms due to their pronounced sociability. However, quantitative assessment of attachment security/insecurity in rodents has been a major challenge. The present study identified attachment insecurity behaviors in rats subjected to maternal separation (MS) during postnatal days (PD) 2-16 and early weaning (EW) during PD 17-21. This MSEW procedure has been used to mimic early life neglect in humans. After MSEW, rats continued to survive until early adulthood when they were subjected to open-field, social interaction, and elevated-plus maze tests. Compared to CNT rats in either gender, MSEW rats moved longer distances at higher velocities in the open-field. The MSEW rats also showed lower ratios of travel distance at central zone over that on whole arena of the open-field compared to CNT rats. In social interaction test, male CNT rats preferred to investigate an empty cage than females; whereas female CNT rats spent more time with a partner-containing cage as compared to males. This gender-specific difference was reversed in MSEW rats. On elevated-plus maze female CNT rats exhibited more risk-taking behaviors as compared to male counterparts. Moreover, female MSEW rats experienced a greater difficulty in making a decision on whether approaching to or averting from which arms of elevated-plus maze. Taken together, male MSEW rats behaved like attachment anxiety while females' phenotype is alike to attachment avoidance described in humans. These results shall prompt further application of MSEW rat in abnormal psychology and biological psychiatry research.

Historical Dynamics of Semi-Humid Evergreen Forests in the Southeast Himalaya Biodiversity Hotspot: A Case Study of the Quercus franchetii Complex (Fagaceae).

The Oligocene and Miocene are key periods in the formation of the modern topography and flora of East Asian and Indo-China. However, it is unclear how geological and climatic factors contributed to the high endemism and species richness of this region. The Quercus franchetii complex is widespread in the southeast Himalaya fringe and northern Indo-China with a long evolutionary history. It provides a unique proxy for studying the diversity pattern of evergreen woody lineages in this region since the Oligocene. In this study, we combined chloroplast (cpDNA) sequences, nuclear microsatellite loci (nSSRs), and species distribution modeling (SDM) to investigate the impacts of geological events on genetic diversity of the Q. franchetii complex. The results showed that the initial cpDNA haplotype divergence was estimated to occur during the middle Oligocene (30.7 Ma), which might have been raised by the tectonic activity at this episode to the Miocene. The nSSR results revealed two major groups of populations, the central Yunnan-Guizhou plateau (YGP) group and the peripheral distribution group when K = 2, in responding to the rapid YGP uplift during the late Miocene, which restricted gene flow between the populations in core and marginal areas. SDM analysis indicated that the distribution ranges of the Q. franchetii complex expanded northwards after the last glacial maximum, but the core distribution range in YGP was stable. Our results showed that the divergence of Q. franchetii complex is rooted in the mid-Oligocene. The early geological events during the Oligocene, and the late Miocene may play key roles to restrict seed-mediated gene flow among regions, but the pollen-mediated gene flow was less impacted. The uplifts of the YGP and the climate since LGM subsequently boosted the divergence of the populations in core and marginal areas.

Temporal Variation in Community Composition of Root Associated Endophytic Fungi and Carbon and Nitrogen Stable Isotope Abundance in Two Bletilla Species (Orchidaceae).

Mycorrhizae are an important energy source for orchids that may replace or supplement photosynthesis. Most mature orchids rely on mycorrhizae throughout their life cycles. However, little is known about temporal variation in root endophytic fungal diversity and their trophic functions throughout whole growth periods of the orchids. In this study, the community composition of root endophytic fungi and trophic relationships between root endophytic fungi and orchids were investigated in Bletilla striata and B. ochracea at different phenological stages using stable isotope natural abundance analysis combined with molecular identification analysis. We identified 467 OTUs assigned to root-associated fungal endophytes, which belonged to 25 orders in 10 phyla. Most of these OTUs were assigned to saprotroph (143 OTUs), pathotroph-saprotroph (63 OTUs) and pathotroph-saprotroph-symbiotroph (18 OTUs) using FunGuild database. Among these OTUs, about 54 OTUs could be considered as putative species of orchid mycorrhizal fungi (OMF). For both Bletilla species, significant temporal variation was observed in the diversity of root endophytic fungi. The florescence and emergence periods had higher fungal community richness of total species and endemic species than did other periods. Both Bletilla species were dominated by Agaricomycetes and Basidiomycota fungi throughout the whole year; however, their abundances varied between two Bletilla species and among phenological stages. Meanwhile, the ranges of 13C and 15N natural abundance were also highly dynamic across all growth stages of Bletilla species. Compared with the surrounding autotrophic plants, significant 13C enrichments (ε13C) were found across all phenological stages, while significant 15N enrichment in the florescence period and strong 15N depletion during the fruiting period were found for both Bletilla species. We can deduce that both Bletilla species obtained carbon from root endophytic fungi during the whole year. Additionally, the temporal varying tendency of root endophytic fungal diversity was consistent with 13C enrichments, which was also accord with the nutritional requirement of plant.

Mapping the Alterations of Glutamate Using Glu-Weighted CEST MRI in a Rat Model of Fatigue.

Objective: Glutamate dysregulation may play an important role in the pathophysiology of fatigue. Glutamate weighted chemical exchange saturation transfer (Glu-weighted CEST) MRI is a recently developed technology which enables measuring glutamate in vivo with high sensitivity and spatial resolution. The purpose of this study is to map the alternations of brain glutamate in a rat model of fatigue. Methods: Rats were subjected to 10 days fatigue loading procedure (fatigue group) or reared without any fatigue loading (control group). Spontaneous activities of rats in the fatigue group were recorded from 3 days before fatigue loading to 4 days after the end of fatigue loading. Glu-weighted CEST were performed following 10-day fatigue loading. Results: Rats in the fatigue group exhibited significant reduced spontaneous activities after 10-day fatigue loading. The glutamate level in the whole brain increased significantly in the fatigue group compared to that in the control group. Further analysis of glutamate in the sub-regions of brain including the prefrontal cortex, hippocampus, and striatum revealed a trend of increment, although statistical significance was not reached. Significance: The increase of glutamate level in the brain may be a crucial process involved in the pathophysiology of fatigue.

Maternal separation with early weaning impairs neuron-glia integrity: non-invasive evaluation and substructure demonstration.

Astrocytes and oligodendrocytes play essential roles in regulating neural signal transduction along neural circuits in CNS. The perfect coordination of neuron/astrocyte and neuron/oligodendrocyte entities was termed as neuron-glia integrity recently. Here we monitored the status of neuron-glia integrity via non-invasive neuroimaging methods and demonstrated the substructures of it using other approaches in an animal model of maternal separation with early weaning (MSEW), which mimics early life neglect and abuse in humans. Compared to controls, MSEW rats showed higher glutamate level, but lower GABA in prefrontal cortex (PFC) detected by chemical exchange saturation transfer and 1H-MRS methods, lower levels of glial glutamate transporter-1 and ATP-α, but increased levels of glutamate decarboxylase-65 and glutamine synthetase in PFC; reduced fractional anisotropy in various brain regions revealed by diffusion tensor imaging, along with increased levels of N-acetyl-aspartate measured by 1H-MRS; and hypomyelination in PFC as evidenced by relevant cellular and molecular changes.

The Prevalence of Dyslexia in Primary School Children and Their Chinese Literacy Assessment in Shantou, China.

The epidemiological studies of Chinese developmental dyslexia (DD) in China are still limited. In addition, literacy assessment has seldom been performed for children with dyslexia, due to lack of uniform assessment tools. This study was aimed at investigating the prevalence rate of children with dyslexia, and to evaluate their Chinese reading ability. A total of 2955 students aged 7-12 years were enrolled by randomized cluster sampling. The study was divided into three stages. In stage I, all participating students were asked to finish the Combined Raven Test (CRT) and Chinese Vocabulary Test and Assessment Scale. In stage II, the Chinese teachers and parents of the children with suspected dyslexia were interviewed by psychiatrists, and finished the Dyslexia Checklist for Chinese Children (DCCC). In stage III, these children were evaluated by child psychiatrists for the diagnosis with or without dyslexia, according to the fifth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and their Chinese literacy was further evaluated by using the Chinese Reading Ability Test (CRAT). The prevalence rate of children with dyslexia was 5.4% in Shantou city, 8.4% in boys and 2.3% in girls, with a gender ratio of 3.7:1.0. Children with dyslexia scored lower in all the five subscales of the CRAT tests. including phonological awareness, morphological awareness, rapid automatized naming, orthographic awareness, and reading ability than the control group (all p < 0.001). This study suggested that the prevalence rate of Chinese dyslexia in Shantou city is roughly equivalent to that previously reported in China. Children with dyslexia have a relatively lower Chinese reading ability in all assessments.

COVID-19 infection outbreak increases anxiety level of general public in China: involved mechanisms and influencing factors.

BACKGROUND: COVID-19 outbreak happened last December in China and is still continuing. Here, we reported effects of COVID-19 outbreak on the mood of general public and ascertained impacts of psychosocial factors on the plague-related emotional measures. METHODS: During Feb. 4-6, 2020, a self-reported questionnaire Beck Anxiety Inventory (BAI) was disseminated to general public via Wechat, along with a sociodemographic information sheet. BAI score and incidences of moderate and severe anxiety in subgroups of respondents were compared. Multiple linear and logistic regressions were done for correlation analysis and to identify factors predictive of anxiety. RESULTS: Averaged BAI score of all respondents is higher than those of general public in two previous studies. The people quarantined for probable COVID-19 infection presented higher BAI score and incidences of moderate and severe anxiety relative to non-quarantined respondents. People in high epidemic area showed higher BAI score and incidences of moderate and severe anxiety compared to those in low epidemic area. Significant associations existed between anxiety level of the respondents and each of the investigated factors, except for gender. Quarantine was the predictor with a highest OR, followed by divorced/widow. The other factors showed smaller but significant effects on the anxiety level of respondents. LIMITATIONS: This cross-sectional study was unable to track the emotional changes in the respondents over time. It had a relatively small sample and involved some of emotional measures only. CONCLUSION: These data are of help in planning psychological interventions for the different subpopulations in general public during and after COVID-19 outbreak.

Compromised Lactate Efflux Renders Vulnerability of Oligodendrocyte Precursor Cells to Metabolic Stresses.

Among the brain cells, oligodendrocyte progenitor cells (OPCs) are the most vulnerable in response to hypoxic and ischemic insults, of which the mechanism remains unknown. Brain cells are known to import or export lactate via differentially expressed monocarboxylate transporters (MCTs) to maintain energy metabolism and pH homeostasis. The present study aims to determine the role of MCT1 in the high vulnerability of OPCs. Here we show that a mild ischemic condition equivalent to ischemic preconditioning caused detectable loss of OPCs. MCT1, which is primarily expressed in oligodendrocyte lineage cells including OPCs, was up-regulated immediately under oxygen-glucose deprivation (OGD) conditions. However, persistent hypoxia, but not hypoglycemia, inhibited the function of MCT1, leading to an intracellular lactate accumulation and acidosis in OPCs. Neurons, which express primarily MCT2, were able to export lactate and maintain an intracellular pH homeostasis under similar conditions. The results support that compromised lactate efflux resulting from hypoxia-induced dysfunction of MCT1 contributes to the high vulnerability of OPCs.

The Long-Term Effects of Adolescent Social Defeat Stress on Oligodendrocyte Lineage Cells and Neuroinflammatory Mediators in Mice.

OBJECTIVE: Adverse childhood and adolescent experiences are associated with the emergences of psychopathology later in life and have negative consequences on white matter integrity. However, this adversity-induced white matter impairment remains not fully investigated. METHODS: Adolescent Balb/c mice were subjected to intermittent social defeat stress once a day during postnatal days 25 to 40. Then, the subjects were allowed to recover for three weeks before sacrifice. At the end, oligodendrocyte (OL) lineage cells, cell proliferation, and microglia activation, as well as myelin basic protein (MBP) levels in frontal cortex and hippocampus were evaluated. The levels of interleukin (IL)-1ß and IL-6 in the brain regions were assessed. RESULTS: MBP protein level in frontal cortex, but not in the hippocampus of defeated mice, decreased significantly compared to controls. The numeral densities of mature OLs, oligodendrocyte progenitor cells, and proliferating cells in medial prefrontal cortex were comparable between the defeated mice and controls. The defeated mice, however, showed significantly higher IL-1ß level, although IL-6 level and numeral density of microglia in frontal cortex did not change relative to controls. CONCLUSION: These results indicate that effects of intermittent social defeat stress on the white matter integrity and OL lineage cells in mouse brain are region- and developmental stage-specific. Upregulated IL-1ß may contribute to this negative consequence though the underlying mechanism remains to be investigated.

Adenosine Promotes the Recovery of Mice from the Cuprizone-Induced Behavioral and Morphological Changes while Effecting on Microglia and Inflammatory Cytokines in the Brain.

Recent studies have shown that multiple sclerosis (MS) and schizophrenia share similarities in some respects, including white matter damage and neuroinflammation. On the other hand, adenosine was reported to promote oligodendrocyte precursor maturation and remyelinating while influencing microglia activation. The aim of the present study was to examine possible beneficial effects of adenosine on the recovery of cuprizone (CPZ)-exposed mouse which has been used as an animal model of MS and schizophrenia as the CPZ-exposed mouse presents demyelination, oligodendrocyte loss, microglia accumulation, as well as behavioral changes. As reported previously, C57BL/6 mice, after fed CPZ for 5 weeks, showed salient demyelination and oligodendrocyte loss in the cerebral cortex (CTX) and hippocampus, in addition to displaying anxiety-like behavior, spatial working memory deficit, and social interaction impairment. Administration of adenosine for 7 days during the recovery period after CPZ withdrawal promoted the behavioral recovery of CPZ-exposed mice and accelerated the remyelinating process in the brains of mice after CPZ withdrawal in a dose-dependent manner. In addition, the effective dose (10 mg/kg) of adenosine inhibited microglia activation and suppressed abnormal elevation of the pro-inflammatory cytokines IL-1ß and TNF-α in CTX and hippocampus, but increased levels of the anti-inflammatory cytokines IL-4 or IL-10 in the same brain regions during the remyelinating process. These results provided an evidence-based rationale for the application of adenosine or its analogues as add-on therapy for schizophrenia.

Facile Preparation of Modifying Layered Double Hydroxide Nanoparticles for Drug Delivery.

Mg-Al-NO3 hydrotalcite (p-LDH) was employed as a carrier for the controlled release of 5-Fluorouracil (5-FU). The p-LDH was pretreated by acid-pretreatment to gain a more stable material (a-LDH) in acid medium for oral administration. It demonstrated that the a-LDH had smaller crystal size, particle sizes and higher permanent charge density (σp) compared with that of the p-LDH by means of XRD, SEM, FT-IR, UV-vis DRS, TG-DSC, BET/BJH and other techniques. The FU/a-LDH and FU/p-LDH delivery systems were obtained using anion-exchange method. The in vitro 5-FU drug release studies showed that no burst release phenomenon was observed at the beginning of release tests. The in vitro 5-FU release behaviors of the delivery systems at initial pH 4.6 and 7.5 were studied which could be described by first-order and Bhaskas models. Combined with the XRD and FT-IR analyses of the solid residues of the FU/a-LDH and FU/p-LDH after the release, it was found that the dissolution mechanism was mainly responsible for the release behavior of the FU/p-LDH at initial 4.6, while the anion-exchange between intercalated 5-FU and phosphate anions mechanism was responsible for the FU/a-LDH at pH 4.6 and 7.5 as well as FU/p-LDH at pH 7.5. It is concluded that the hydrotalcites could be used as the basis of a tunable drug delivery carrier for 5-FU.

N-acetylcysteine attenuates the cuprizone-induced behavioral changes and oligodendrocyte loss in male C57BL/7 mice via its anti-inflammation actions.

Previous animal studies have linked white matter damage to certain schizophrenia-like behaviors in cuprizone (CPZ)-exposed mouse. Mitochondrial dysfunction, oxidative stress, neuroinflammation, and oligodendrocyte loss coexist in the brain of such mice. The aim of this study was to examine effects of the antioxidant N-acetylcysteine (NAC) on CPZ-induced behavioral changes and concurrent oligodendrocyte loss, oxidative stress, and neuroinflammation in these animals. Male C57BL/6 mice were given intraperitoneal saline or NAC at doses of 100, 200, and 400 mg/kg/day for 2 weeks; animals were fed a CPZ-containing diet (0.2%, w/w) during days 5-14. During days 15-17, the mice were examined in open-field, social recognition, and Y-maze tests (1 test per day). Six mice in each group were then used for biochemical and enzyme-linked immunosorbent assay analyses, while the remaining animals were used for immunohistochemical and immunofluorescence staining. The mice exposed to CPZ for 10 days showed significantly lower spontaneous alternation in the Y-maze, lower activity of total superoxide dismutase, and glutathione peroxidase, but higher levels of malondialdehyde in the cerebral cortex and hippocampus, elevated concentrations of interleukin-1ß and tumor necrosis factor-α in the brain regions mentioned above and caudate putamen, and a decreased number of mature oligodendrocytes, but increased number of microglia in all the brain regions examined. These changes, however, were not seen or effectively alleviated in NAC-treated mice at all three doses. These results demonstrate that NAC protected mature oligodendrocytes against the toxic effects of CPZ, likely via its antioxidant and anti-inflammatory actions.

Monocarboxylate transporter 1 and the vulnerability of oligodendrocyte lineage cells to metabolic stresses.

AIMS: Oligodendrocytes, especially oligodendrocyte precursor cells, are known to be sensitive to hypoxic and metabolic stresses. Vulnerability of oligodendrocytes is considered a contributing factor to white matter dysfunction. However, little is known about the energy processing characteristics of oligodendrocyte lineage cells under basal and metabolic stress conditions. The aim of this study was to identify the energy requirements and cellular responses of oligodendrocytes at different developmental stages. METHODS: We compared the metabolic stress responses between myelinating oligodendrocytes (OLs) and oligodendrocyte precursor cells (OPCs). Differential regulation of cellular response was also investigated. RESULTS: We found that, following cerebral ischemia, monocarboxylate transporter 1 (MCT1) expression was upregulated in the peri-infarct striatum but not in the cortex of the brain. In vitro ischemia models were used to induce oligodendrocyte stress as well. An increase in MCT1 expression was detected in OPCs after a mild oxygen-glucose deprivation. Double-labeled immunohistochemical analysis revealed that OPCs and OLs responded differently to metabolic stresses and that the susceptibility to metabolic stresses of OPCs and OLs was associated with their distinct expression profiles of MCT1. CONCLUSION: Taken together, this study shows that MCT1 plays a role in the responses of OPCs and OLs to metabolic and ischemic stresses and suggests that redistribution of energy substrates is a determinant in white matter injury.

Artesunate prevents rats from the clozapine-induced hepatic steatosis and elevation in plasma triglycerides.

Clozapine is an atypical antipsychotic with therapeutic efficacy in treatment-resistant schizophrenia patients and low incidence of extrapyramidal side effects. However, the use of clozapine has been limited by its adverse effects on metabolism. Artesunate is a semisynthetic derivative of artemisinin and was shown to decrease the plasma cholesterol and triglyceride in rabbits and rats in recent studies. The aim of this study was to examine possible effects of artesunate on the clozapine-induced metabolic alterations in rats given saline, clozapine, artesunate, or clozapine plus artesunate for 6 weeks. The clozapine group showed significantly high plasma levels of triglyceride, hepatic steatosis, and fibrosis along with high levels of C-reactive protein, alanine aminotransferase, and aspartate aminotransferase compared to the saline group. But the treatment had no effect on weight gain and caused no hyperglycemia, hyperinsulinemia, and behavioral changes in the rats. More significantly, these clozapine-induced changes were not seen in rats coadministered with clozapine plus artesunate. These results added evidence supporting psychiatrists to try add-on treatment of artesunate in schizophrenia patients to ameliorate clozapine-induced adverse metabolic effects.