Treadmill Running Regulates Adult Neurogenesis, Spatial and Non-spatial Learning, Parvalbumin Neuron Activity by ErbB4 Signaling.

Exercise can promote adult neurogenesis and improve symptoms associated with schizophrenia and other mental disorders via parvalbumin (PV)-positive GABAergic interneurons in the dentate gyrus ErbB4 is the receptor of neurotrophic factor neuregulin 1, expressed mostly in PV-positive interneurons. Whether ErbB4 in PV-positive neurons mediates the beneficial effect of exercise and adult neurogenesis on mental disorder needs to be further investigation. Here, we first conducted a four-week study on the effects of AG1478, an ErbB4 inhibitor, on memory and neurogenesis. AG1478 significantly impaired the performance in several memory tasks, including the T-maze, Morris water maze, and contextual fear conditioning, downregulated the expression of total ErbB4 (T-ErbB4) and the ratio of phosphate-ErbB4 (p-ErbB4) to T-ErbB4, and associated with neurogenesis impairment. Interestingly, AG1478 also appeared to decrease intracellular calcium levels in PV neurons, which could be reversed by exercise. These results suggest exercise may regulate adult neurogenesis and PV neuron activity through ErbB4 signaling. Overall, these findings provide further evidence of the importance of exercise for neurogenesis and suggest that targeting ErbB4 may be a promising strategy for improving memory and other cognitive functions in individuals with mental disorders.

[Factors Influencing and Adverse Reactions of Voriconazole Clearance in Patients with Hematological Diseases].

OBJECTIVE: To monitor the changes of voriconazole minimum concentration(Cmin) in patients with hematological diseases, and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases, so as to provide a theoretical basis for reasonable clinical use of voriconazole. METHODS: 136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected. The correlation between C-reactive protein, albumin, creatinine and voriconazole Cmin were analyzed, and the changes of voriconazole Cmin after glucocorticoid treatment was also detected. In addition, stratified analysis was used to explore the adverse events of voriconazole. RESULTS: Among 136 patients, 77 were male (56.62%) and 59 were female (43.38%). There were positive correlations between voriconazole Cmin and C-reactive protein and creatinine levels (r=0.277, r=0.208), while voriconazole Cmin was negatively correlated with albumin level (r=-2.673). Voriconazole Cmin in patients treated with glucocorticoid was decreased significantly (P<0.05). In addition, sratified analysis of voriconazole Cmin showed that compared with voriconazole Cmin 1.0-5.0 mg/L group, the incidence of adverse reactions of visual impairment in voriconazole Cmin> 5.0 mg/L group was increased (χ2=4.318, P=0.038). CONCLUSION: The levels of C-reactive protein, albumin and creatinine are closely related to the voriconazole Cmin, which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases. It is necessary to monitor the voriconazole Cmin of patients with hematological diseases, and adjust the dosage in time to reduce adverse reactions.

Parvalbumin Interneuron Activation-Dependent Adult Hippocampal Neurogenesis Is Required for Treadmill Running to Reverse Schizophrenia-Like Phenotypes.

Physical exercise can alleviate some of the schizophrenia symptoms in patients, the mechanisms, however, are still unclear. To investigate whether the GABAergic interneuron involved in the therapeutic effect of treadmill running on schizophrenia, the parvalbumin (PV)-positive GABAergic interneurons in the dentate gyrus (DG) was specifically activated or abolished and the effects were evaluated. In the MK801-induced schizophrenia-like animal model, we found:(1) Treadmill running rescued the schizophrenia-related behavioral phenotypes, promoted the adult hippocampal neurogenesis, and increased the dendrite number and complexity of newborn neurons. (2) Treadmill running increased the number of PV-positive interneurons in the DG; genetic ablation of these interneurons reduced adult neurogenesis and abolished the effect of treadmill running on the schizophrenia-related behaviors. Consistently, chemogenetic activation of these interneurons improved neurogenesis and alleviated the schizophrenia-related behaviors. These results suggest a pivotal role of PV-positive interneuron-mediated adult neurogenesis in exercise. (3) However, schizophrenia-related behavioral phenotypes and adult neurogenesis in the DG could still be reversed by exercise after specifically knocking out the schizophrenia-related gene ErbB4 in PV interneurons, as a means to reduce their GABA release. These results suggest that activation of PV interneurons in the DG is sufficient for treadmill running to reverse schizophrenia-like phenotypes.