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Although the brain–gut axis appears to play a role in the pathogenesis of Parkinson’s disease, the precise mechanisms underlying the actions of gut microbiota in this disease are unknown. This study was undertaken to investigate whether antibiotic-induced microbiome depletion affects dopaminergic neurotoxicity in the mouse brain after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPTP significantly decreased dopamine transporter (DAT) immunoreactivity in the striatum and tyrosine hydroxylase (TH) immunoreactivity in the substantia nigra of water-treated mice. However, MPTP did not decrease DAT or TH immunoreactivity in the brains of mice treated with an antibiotic cocktail. Furthermore, antibiotic treatment significantly decreased the diversity and altered the composition of the host gut microbiota at the genus and species levels. Interestingly, MPTP also altered microbiome composition in antibiotic-treated mice. These findings suggest that antibiotic-induced microbiome depletion might protect against MPTP-induced dopaminergic neurotoxicity in the brain via the brain–gut axis.

In rodent models of depression, (R)-ketamine has greater potency and longer-lasting antidepressant effects than (S)ketamine; however, the precise molecular mechanisms underlying the antidepressant actions of (R)-ketamine remain unknown. Using RNA-sequencing analysis, we identified novel molecular targets that contribute to the different antidepressant effects of the two enantiomers. Either (R)-ketamine (10 mg/kg) or (S)-ketamine (10 mg/kg) was administered to susceptible mice after chronic social defeat stress (CSDS). RNA-sequencing analysis of prefrontal cortex (PFC) and subsequent GSEA (gene set enrichment analysis) revealed that transforming growth factor (TGF)-β signaling might contribute to the different antidepressant effects of the two enantiomers. (R)-ketamine, but not (S)-ketamine, ameliorated the reduced expressions of Tgfb1 and its receptors (Tgfbr1 and Tgfbr2) in the PFC and hippocampus of CSDS susceptible mice. Either pharmacological inhibitors (i.e., RepSox and SB431542) or neutralizing antibody of TGF-β1 blocked the antidepressant effects of (R)-ketamine in CSDS susceptible mice. Moreover, depletion of microglia by the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX3397 blocked the antidepressant effects of (R)-ketamine in CSDS susceptible mice. Similar to (R)-ketamine, the recombinant TGF-β1 elicited rapid and long-lasting antidepressant effects in animal models of depression. Our data implicate a novel microglial TGF-β1-dependent mechanism underlying the antidepressant effects of (R)-ketamine in rodents with depression-like phenotype. Moreover, TGF-β1 and its receptor agonists would likely constitute a novel rapid-acting and sustained antidepressant in humans.

Background Suffering from COVID-19 is a strong psychological stressor to the patients. Even after recovery, patients are prone to a variety of mental health problems. Recently, some studies focus on the psychological situation of patients when they got COVID-19. However, no study focused on the psychological status of recovered COVID-19-infected patients in China. Our study aims to investigate sleep and mood status, and detect the influencing factors of the psychological status of the COVID-19 patients after recovery. Methods One hundred and twenty-five COVID-19 patients were enrolled from February to April 2020. The social demographic information of all participants was collected by a self-designed questionnaire. Insomnia and depression symptoms were evaluated through the Insomnia Severity Index (ISI) and the Center for Epidemiology Scale for Depression (CES-D). Results The rates of insomnia and depression were 26.45% and 9.92% in the COVID-19 patients after recovery. There were significant differences in physical, mental impairment, and the need for psychological assistance between the COVID-19 recovered patients with depression and the patients without depression. In addition, age and health status may be the influencing factors for insomnia, and care about the views of others may be the influencing factor of depression (P<0.05). Conclusions Based on the results, we found that COVID-19 recovered patients had a low rate of depression and a high rate of insomnia. We need to pay more attention to their sleep condition than mood status.

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Maternal infection during pregnancy increases risk of neurodevelopmental disorders such as schizophrenia and autism spectrum disorder (ASD) in offspring. In rodents, maternal immune activation (MIA) yields offspring with schizophrenia-and ASD-like behavioral abnormalities. Soluble epoxide hydrolase (sEH) plays a key role in inflammation associated with neurodevelopmental disorders. Here we found higher levels of sEH in the prefrontal cortex (PFC) of juvenile offspring after MIA. Oxylipin analysis showed decreased levels of epoxy fatty acids in the PFC of juvenile offspring after MIA, supporting increased activity of sEH in the PFC of juvenile offspring. Furthermore, expression of sEH (or EPHX2) mRNA in induced pluripotent stem cellderived neurospheres from schizophrenia patients with the 22q11.2 deletion was higher than that of healthy controls. Moreover, the expression of EPHX2 mRNA in postmortem brain samples (Brodmann area 9 and 40) from ASD patients was higher than that of controls. Treatment with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), a potent sEH inhibitor, in juvenile offspring from prenatal day (P) 28 to P56 could prevent cognitive deficits and loss of parvalbumin (PV) immunoreactivity in the medial PFC of adult offspring after MIA. In addition, dosing of TPPU to pregnant mothers from E5 to P21 could prevent cognitive deficits, and social interaction deficits and PV immunoreactivity in the medial prefrontal cortex of juvenile offspring after MIA. These findings suggest that increased activity of sEH in the PFC plays a key role in the etiology of neurodevelopmental disorders in offspring after MIA. Therefore, sEH represents a promising prophylactic or therapeutic target for neurodevelopmental disorders in offspring after MIA. epoxy fatty acid | ER stress | iPSCs | maternal infection | prevention E pidemiological studies implicate prenatal environmental factors, including maternal immune activation (MIA), in playing a key role in the etiology of neurodevelopmental disorders such as schizophrenia and autism spectrum disorder (ASD) (1-7). A number of studies suggest associations between maternal infections or inflammatory biomarkers and schizophrenia and ASD (2-4, 7). For example, there are key epidemiological results supporting associations between maternal infectious pathogens (i.e., influenza virus, herpes simplex virus, Toxoplasma gondii, rubella, and bacterial pathogens) and inflammatory biomarkers (i.e., cytokines and Creactive protein) and schizophrenia (2,7,8). The Finnish Prenatal Studies birth cohort showed that elevated maternal levels of Creactive protein in early to midgestation was related to an increased risk of ASD in offspring (9), although maternal midpregnancy levels of C-reactive protein were related to a decreased risk of ASD (10). A meta-analysis suggests that maternal infection during pregnancy increases the risk of ASD in offspring (4). Collectively, MIA during pregnancy can increase the risk of neurodevelopmental disorders in offspring. The onset of schizop...

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