Inhibition of miR-128 Abates Aβ-Mediated Cytotoxicity by Targeting PPAR-γ via NF-κB Inactivation in Primary Mouse Cortical Neurons and Neuro2a Cells

PURPOSE: Alzheimer's disease (AD) is the sixth most common cause of death in the United States. MicroRNAs have been identified as vital players in neurodegenerative diseases, including AD. microRNA-128 (miR-128) has been shown to be dysregulated in AD. This study aimed to explore the roles and molecular mechanisms of miR-128 in AD progression. MATERIALS AND METHODS: Expression patterns of miR-128 and peroxisome proliferator-activated receptor gamma (PPAR-γ) messenger RNA in clinical samples and cells were measured using RT-qPCR assay. PPAR-γ protein levels were determined by Western blot assay. Cell viability was determined by MTT assay. Cell apoptotic rate was detected by flow cytometry via double-staining of Annexin V-FITC/PI. Caspase 3 and NF-κB activity was determined by a Caspase 3 Activity Assay Kit or NF-κB p65 Transcription Factor Assay Kit, respectively. Bioinformatics prediction and luciferase reporter assay were used to investigate interactions between miR-128 and PPAR-γ 3′UTR. RESULTS: MiR-128 expression was upregulated and PPAR-γ expression was downregulated in plasma from AD patients and amyloid-β (Aβ)-treated primary mouse cortical neurons (MCN) and Neuro2a (N2a) cells. Inhibition of miR-128 decreased Aβ-mediated cytotoxicity through inactivation of NF-κB in MCN and N2a cells. Moreover, PPAR-γ was a target of miR-128. PPAR-γ upregulation attenuated Aβ-mediated cytotoxicity by inactivating NF-κB in MCN and N2a cells. Furthermore, PPAR-γ downregulation was able to abolish the effect of anti-miR-128 on cytotoxicity and NF-κB activity in MCN and N2a cells. CONCLUSION: MiR-128 inhibitor decreased Aβ-mediated cytotoxicity by upregulating PPAR-γ via inactivation of NF-κB in MCN and N2a cells, providing a new potential target in AD treatment.

Changes of cholinergic neurons in the hippocampus of vascular dementia rats after neural stem cell transplantation / 中国组织工程研究

each group were sacrificed, respectively. Distributions of BrdU positive cels and ChAT positive cels were detected by S-P immunohistochemical method. The learning and memory abilities of rats were detected by Morris water maze system. RESULTS AND CONCLUSION:BrdU positive cels were mainly distributed in the cortex and hippocampus, especialy around the blood vessels, and there was the presence of focal aggregation. A smal amount of BrdU positive cels were observed in the basal ganglia and thalamus as wel as in the ependyma. BrdU positive cels were counted at different time after operation. The number of BrdU positive cels decreased with time, and only a smal number of BrdU positive cels were observed at 60 days after transplantation. The number of ChAT positive cels at different time after transplantation was ranked as folows: neural stem cel transplantation group > model group > sham operated group (P < 0.05). Compared with the model group, the time for searching the platform was significantly lower in the neural stem transplantation group and sham operated group, but the number of crossing the platform was significantly higher in the neural stem cel transplantation group and sham operated group (P < 0.05). The results show that neural stem cels could be transplanted into the rats with vascular dementia, and the cels could survive and migrate in the brain of rats and significantly improve the learning and memory ability. This mechanism may be related to the differentiation and growth of cholinergic neurons in the hippocampus.

Therapeutic effect of oral exercise method combined with shaker exercise on dysphagia in patients with cere-bral hemorrhage / 中国基层医药

Objective To investigate the effect of oral exercise method combined with shaker exercise on dysphagia in patients with cerebral hemorrhage.Methods 112 patients with dysphagia caused by cerebral hemor-rhage were randomly divided into control group (28 cases,conventional treatment),oral exercise method group (28 cases,conventional treatment combined with oral exercise method),shaker exercise group (28 cases,conventional treatment combined with shaker exercise)and combination group (28 cases,conventional treatment combined with oral exercise method and shaker exercise).Four groups were assessed with video fluoroscopic swallowing study (VF-SS)before treatment and after treatment.Results (1)There were no differences on VFSS among four groups before treatment (P >0.05).After treatment,there were significant differences on VFSS among four groups(F =9.40,P 0.05).In the remaining groups,the scores of VFSS after treatment were significant higher than that of before treatment (P <0.05).(2)The total effective rate in combination group was higher than that of the remaining groups(χ2 =37.76,P <0.01).Combination group (96.43%)combined with the highest total effective rate,followed by shaker exercise group (75.00%)and oral exercise method group (71.43%),control group (21.42%)combined with the lowest total effective rate.Conclusion The application of oral exercise method combined with shaker exercise on patients with dysphagia caused by cerebral hemorrhage could improve the swallowing function.