Inhibition of MiR-122 Decreases Cerebral Ischemia-reperfusion Injury by Upregulating DJ-1-Phosphatase and Tensin Homologue Deleted on Chromosome 10 (PTEN)/Phosphonosinol-3 Kinase (PI3K)/AKT.

BACKGROUND Ischemia-reperfusion injury is caused by a blood reperfusion injury in ischemic brain tissue, and usually occurs in the treatment stage of ischemic disease, which can aggravate brain tissue injury. MiR-122 is closely related to ischemia-reperfusion injury in the myocardium, kidney, and liver; however, the role in cerebral ischemia-reperfusion injury has not been established. MATERIAL AND METHODS In this study, cerebral ischemia-reperfusion injury was established in a rat model, and the control group was a sham-operated group. After ischemia-reperfusion injury for 6, 12, and 24 hours, brain tissue specimens were collected and the expression of miR-122 and DJ-1 were determined using quantitative real-time polymerase chain reaction. Flow cytometry was used to determine the reactive oxygen species (ROS) content. The modified Neurological Severity Score (mNSS) scale was used to evaluate the sensory and motor function defects of the rats. The malondialdehyde (MDA), superoxide dismutase (SOD), and enzyme activity were determined. The rats in the cerebral ischemia-reperfusion injury model were divided into 2 groups (antagomir-NC group and antagomir miR-122 group). Brain neuron RN-c cells were divided into the following 4 groups: antagomir-NC, antagomir miR-122, pIRES2-blank, and pIRES2-DJ-1. Seventy-two hours after transfection, ischemia-reperfusion treatment was carried out and conventional cultured RN-c cells were used as the control group. Flow cytometry was used to detect apoptosis and western blot was used to detect the expression of DJ-1, PTEN, AKT, and p-AKT. RESULTS The expression of miR-122 increased significantly in the process of ischemia-reperfusion damage after cerebral infarction, while the expression of DJ-1 decreased significantly. Downregulation of miR-122 significantly increased the expression of DJ-1, enhanced the activity of the PTEN/PI3K/AKT pathway, reduced cell apoptosis, and alleviated cerebral ischemia-reperfusion injury. CONCLUSIONS Inhibition of miR-122 can decrease cerebral ischemia-reperfusion injury by upregulating DJ-1-PTEN/PI3K/AKT pathway.

Orexin-A exacerbates Alzheimer's disease by inducing mitochondrial impairment.

Alzheimer's disease (AD) is a progressive neurodegenerative disease which is characterized by the accumulation of amyloid-ß peptide (Aß). Orexin-A is a neuropeptide which has been reported to participate in the pathogenesis of AD. Thus, we aimed to investigate the possible mechanism by which Orexin-A acts in AD. APP/PS1 transgenic mice, an animal model of AD, were intracerebroventricularly injected with Orexin-A. Aß-treated SH-SY5Y cells were used as a cell model of AD and treated with Orexin-A. The Morris water maze test, fluorescence microscopy, enzyme-linked immunosorbent assay (ELISA), electron microscopy, real-time PCR, and other biochemical assays were conducted. The Morris water maze test showed that Orexin-A aggravated cognitive deficit in APP/PS1 mice. Using thioflavine-S staining and ELISA, we found that Orexin-A promoted Aß accumulation in APP/PS1 mice. By evaluating mitochondrial morphology, cytochrome c oxidase activity, ATP level, mitochondrial DNA copy number, and reactive oxygen species, we found that Orexin-A aggravated mitochondrial impairment in APP/PS1 mice and Aß-treated SH-SY5Y cells. Our results indicate that Orexin-A exacerbates AD by inducing mitochondrial impairment. This is a new mechanism that explains how Orexin-A participates in the pathogenesis of AD.

The Promising Effects of Transplanted Umbilical Cord Mesenchymal Stem Cells on the Treatment in Traumatic Brain Injury.

Many studies have reported the recovery ability of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for neural diseases. In this study, the authors explored the roles of UC-MSCs to treat the traumatic brain injury. Umbilical cord-derived mesenchymal stem cells were isolated from healthy neonatal rat umbilical cord immediately after delivery. The traumatic brain injury (TBI) model was formed by the classical gravity method. The authors detected the behavior changes and measured the levels of inflammatory factors, such as interleukin-lß and tumor necrosis factor-α by enzyme linked immunosorbent assay (ELISA) at 1, 2, 3, 4 weeks after transplantation between TBI treated and untreated with UC-MSCs. Simultaneously, the expression of glial cell line-derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF) were measured by real-time-polymerase chain reaction and ELISA.The authors found that the group of transplantation UC-MSCs has a significant improvement than other group treated by phosphate buffered saline. In the behavioral test, the Neurological Severity Scores of UC-MSCs + TBI group were lower than TBI group (P < 0.05), but not obviously higher than control group at 2, 3, and 4week, respectively. The inflammatory factors are significantly reduced comparison with TBI group (P < 0.05), but both GDNF and BDNF were higher than TBI group (P < 0.05). The results indicated that UC-MSCs might play an important role in TBI recovery through inhibiting the release of inflammatory factors and increasing the expression of GDNF and BDNF.

Baicalein ameliorated the upregulation of striatal glutamatergic transmission in the mice model of Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disorder, which is characterized by a loss of projecting dopaminergic neurons in the substantia nigra and diminished dopamine level in the striatum. Dopaminergic deficit consequently leads to the alterations of striatal basal glutamatergic synaptic transmission and plasticity in the medium spiny neurons. The cytokines and neurotoxins released from the reactive immune cells induced the loss of the projecting dopaminergic neurons in the substantia nigra, which triggering the pathogenesis of PD. The present study investigated the effect of treatment with baicalein (5,6,7-trihydroxyflavone) on the central cytokine synthesis, striatal glutamatergic transmission, and behavioral performance in the rotarod task in the mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Treatment with baicalein significantly attenuated the upregulation of striatal basal glutamatergic strength by decreasing the presynaptic glutamate release and recovering the insertion of postsynaptic glutamate receptor subunit GluR1 induced by MPTP. It also significantly improved the behavioral performance in the rotarod task in the mice injected with MPTP. Treatment with baicalein decreased the upregulation of cytokines (tumor necrosis factor-α and interleukin-1ß) in the substantia nigra and striatum in the mice injected with MPTP. These results indicated that baicalein might serve as novel approach for the treatment of the patients with PD.