[A pilot study of transcranial alternating current stimulation in the treatment of drug-naive adult patients with major depressive disorder].

Objective: To explore the efficacy, adverse reactions, feasibility, and acceptability of transcranial alternating current stimulation (tACS) treating drug-naive adult patients with major depressive disorder (MDD), and provide basis for further study with a large sample. Methods: The study was performed in the Neuromodulation laboratory, Department of Neurology of Xuanwu Hospital, Capital Medical University (Beijing, China) from July, 2017 to June, 2018. Thirty Eligible first-episode MDD outpatients were randomized 1∶1 to receive active tACS or sham intervention. The tACS was administered in a 40 minute, 77.5 Hz frequency, 15 mA session with one forehead (Fp1, Fpz, and Fp2, in the 10/20 international placement system, 4.45 cm×9.53 cm) and two mastoid (3.18 cm×3.81 cm) stimulation for 20 times in 4 consecutive weeks at fixed day time frame once daily from Monday through Friday, with weekends off (week 4), followed by 4 weeks with no tACS treatment (week 8). By utilizing the Hamilton rating scale for depression-17 item (HRSD-17) to assess the depressive severity of MDD patients, adverse events were administered by the treatment-emergent adverse events, the Young mania rating scale, and the self-made common questionnaire on cranial electrical stimulation. The primary efficacy outcome was the remission rate defined as HRSD-17 score ≤7 at week 8. Secondary outcomes included the rates of remission at week 4 and response at weeks 4 and 8. Safety was assessed by evaluation of adverse events. Also the proportions of participants accepting the intervention and this study procedure were evaluated at weeks 4 and 8. Results: Thirty MDD patients completed the study, and both groups had no statistical differences on their demographic characteristics (P>0.05). At week 8, the active group had a remission rate of 10/15, which was higher than 3/15 in the sham group (P<0.05). Also, the remission rate (14/15) in the active group was higher than 5/15 of the sham group at week 4 (P<0.05). For the response rates, significant differences were found between groups at week 8. For safety, both groups showed no severe adverse events and no mania/hypomania. One participant per group had 2 times of tinnitus cerebri during the intervention days. All patients accepted the intervention and the study procedure. Conclusions: The pilot study indicated that tACS with 77.5 Hz and 15 mA may have a therapeutic effect on depressive symptoms. It is well-tolerated and safe, as well as feasible and acceptable for adults with MDD.

Inhibition of JMJD6 expression reduces the proliferation, migration and invasion of neuroglioma stem cells.

Neuroglioma is the most common form of human primary malignant brain tumor, more and more studies recently showed only a small subpopulation of glioma cells which called glioma stem cells have true tumorigenic potential. Meanwhile, it was reported the overexpression of JMJD6 protein is closely involvement with the occurrence and development of multiple tumors, and JMJD6 is required for the differentiation of multiple organ, tissues and cells during embryogenesis. However, the influence of JMJD6 overexpression on neuroglioma development is unclear now. Hence, to explore the effects of JMJD6 expression on neuroglioma, we firstly isolated glioma stem cells by using CD133 MicroBead Kit, and identified via neurosphere-forming assay and Immunofluorescence staining. At the same time, we investigated the effects and mechanism of JMJD6 on the proliferation, migration and invasion of glioma stem cells through MTT, transwell assays and the Cignal finder cancer 10-pathway reporter array. The results demonstrated that the glioma neurosphere cells positively expressed stem cell marker SOX2, neuroectodermal stem cell marker Nestin, and also expressed astrocytes marker GFAP and neurons marker ß-tubulin III fter FBS-induced differentiation for a week, which proved the glioma neurosphere cells have the self-renewal and multipotential differentiation capacity. Moreover, shRNA lentiviral vector mediated knockdown of JMJD6 in glioma stem cells led to decreased proliferation, migration and invasion, the underlying molecular mechanism is related to the weaken of Wnt signaling pathway and strengthen of p53 signaling pathway.

Temporal and spatial expression of preprotachykinin A mRNA in the developing filial mice brain after maternal administration of monosodium glutamate at a late stage of pregnancy.

In the early stages of brain development, exposure of excessive monosodium glutamate (MSG) to neurons causes animal functional and behavioral disorders in adulthood. To investigate the effects of excessive MSG during pregnancy on the neurons in the developing brain, in situ hybridization was used. In mice, the expression of preprotachykinin A mRNA (PPT A mRNA) was assessed in neurons of in the brain after MSG treatment. Brain tissue sections were hybridized with specific digoxigenin-labeled RNA probes. The number of cells that expressed PPT A mRNA gradually decreased from 10-day-old (10d) to 60-day-old (60d) MSG-treated and normal animals. In the MSG-treated and normal mice, the PPT A mRNA-positive neurons almost disappeared in 90-day-old (90d) mice. The expression of PPT A mRNA significantly decreased at 10d in most of the brain regions of MSG-treated mice including the cerebral cortex (CC), hippocampal subregions of CA1, CA2 (CA1, CA2), habenula nucleus (HAB), hypothalamic periventricular nucleus (PE), hypothalamic arcuate nucleus (AR), median eminence (ME), amygdala nucleus (AMY), endopiriform nucleus (EN), and hypothalamic ventromedial nucleus (VMH) and dorsomedial nucleus (DMH). In the hippocampal CA4 subregions (CA4), paraventricular nucleus (PV) and caudate putamen (CPU), however, they were not significantly altered. Furthermore, in CC, hippocampal CA3 subregion (CA3), PE and EN regions the number of PPT A mRNA-positive neurons decreased at 20 days old (20d), but increased significantly in CA2 and CPU. At 30 days old (30d), the positive neuron number decreased in AMY, and they did not change in other regions. At 60d, the number of positive neurons significantly decreased in PV and ME, but increased in AMY. In the other observed regions, no changes were found. These results show that maternal administration of excessive MSG at a late stage of pregnancy significantly decreases PPT A mRNA expression in most of the brain regions of filial mice. This suggests that glutamate-induced excitotoxicity may affect the metabolism of precursors of substance P in developing brain neurons. The present study provides insights into the plasticity and vulnerability of neuron in different brain regions to glutamate excitotoxicity.