Resveratrol Promotes Autophagy to Improve neuronal Injury in Parkinson's Disease by Regulating SNHG1/miR-128-3p/SNCA Axis.

BACKGROUND: Parkinson's disease (PD) is seriously threatening the health and life quality of the elderly, who have a high incidence and high disability rate. Resveratrol (RES) was reported to play a protective role in PD. However, the functions and potential mechanism of RES in PD remain unclear, which need to be further explored. METHODS: Human neuroblastoma cells (SH-SY5Y and SK-N-SH) were subjected to 1-Methyl-4-phenylpyridium (MPP+) induction to construct a cell model of PD. Cell viability was evaluated using CCK-8. The gene expression was evaluated using qRT-PCR and western blot. Luciferase activity assay and RIP were performed to validate interactions among SNHG1, miR-128-3p and SNCA. RESULTS: Our results exhibited that RES reduced SNHG1 and SNCA expression but elevated miR-128-3p expression in human neuroblastoma cells upon MPP+ induction. Functionally, RES resulted in the promotion of cell autophagy in MPP+-induced human neuroblastoma cells, while these influences were abolished by SNHG1 overexpression. Mechanistically, SNHG1 could indirectly elevate SNCA expression via sponging miR-128-3p. Moreover, SNCA overexpression reversed SNHG1 silencing-induced cell autophagy in MPP+-induced human neuroblastoma cells upon RES pre-incubation. CONCLUSIONS: RES prevented MPP+-induced repression of cell autophagy through inhibiting the SNHG1/miR-128-3p/SNCA axis, suggesting that RES might play a preventive effect on PD progression.

Astaxanthin suppresses endoplasmic reticulum stress and protects against neuron damage in Parkinson's disease by regulating miR-7/SNCA axis.

Parkinson's disease (PD) is a common neurodegenerative disorder that featured by the loss of dopaminergic neurons. Astaxanthin (AST), an important antioxidant, is demonstrated to be a neuroprotective agent for PD. However, the underlying mechanisms of AST in PD remain largely unclear. In this study, we found that AST treatment significantly not only abolished the cell viability inhibition and apoptosis promotion induced by 1-methyl-4-phenylpyridinium (MPP+) in SH-SY5Y cells via inhibiting endoplasmic reticulum (ER) stress, but also reversed the MPP+ caused dysregulation of miR-7 and SNCA expression. MiR-7 knockdown and SNCA overexpression were achieved by treating SH-SY5Y cells with miR-7 inhibitor and pcDNA3.1-SNCA plasmids, respectively. MiR-7 could bind to and negatively regulate SNCA in SH-SY5Y cells. Treated SH-SY5Y cells with miR-7 inhibitor or pcDNA3.1-SNCA abrogated the protective effects of AST on MPP+ induced cytotoxicity. Knockdown of miR-7 aggravated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced neuron injury in vivo suggested by athletic performance, histopathological morphology, expression of tyrosine hydroxylase (TH) and TUNEL positvie cells, however, AST treatment could reverse these effects of miR-7 knockdown. Collectively, AST suppressed ER stress and protected against PD-caused neuron damage by targeting miR-7/SNCA axis, implying that AST might be a potential effective therapeutic agent for PD.

Effect of ginkgolide B on brain metabolism and tissue oxygenation in severe haemorrhagic stroke.

Ginkgolide B, a diterpene, is an herbal constituent isolated from the leaves of Ginkgo biloba tree. The present study demonstrates the effect of ginkgolide B in osmotherapy on brain metabolism and tissue oxygenation. Multimodality monitoring including intracranial pressure (ICP), cerebral perfusion pressure (CPP), partial pressure of brain tissue oxygen (PbtO2), lactate/pyruvate ratio (LPR) and microdialysis were employed to study the effect of ginkgolide B osmotherapy. The results demonstrated that administration of 15% solution of ginkgolide B to the comatose patients with raised ICP (> 20 mm Hg) and resistant to standard therapy led to a significant decrease in ICP. The cerebral microdialysis was used to compare mean arterial blood pressure (MAP), ICP, CPP, PbtO2, brain lactate, pyruvate and glucose level after hourly intervals starting 3 h before and up to 4 h after hyperosmolar therapy. There was a decrease in ICP in 45 min from 23 ± 14 mm Hg (P < 0.001) to 18 ± 24 mm Hg and increase in CPP after 1 h of gingkolide B infusion from 74 ± 18 to 85 ± 22 mm Hg (P < 0.002). However there was no significant effect on MAP but PbtO2 was maintained in the range of 22-26. The peak lactate/pyruvate ratio was recorded at the time of initiation of osmotherapy (44 ± 20) with an 18% decrease over 2 h following gingkolide B therapy. Also the brain glucose remained unaffected.

[Changes in plasma content of matrix metallo proteinase-9 in acute cerebral infarction patients before and after thrombolytic therapy and its significance].

OBJECTIVE: To investigate the changes in the content of plasma matrix metallo proteinase-9 (MMP-9) in patients with acute cerebral infarction before and after thrombolytic therapy and its clinical significance. METHODS: The levels of MMP-9 were determined in 34 patients with acute cerebral infarction before and after thrombolytic therapy, and 34 healthy individuals served as healthy control. RESULTS: Compared with the healthy controls, the levels of plasma MMP-9 before thrombolytic therapy were not significantly increased [(13.47±3.09) ng/L vs. (12.89±10.22) ng/L, P >0.05]. In contrast, MMP-9 values were significantly increased after thrombolytic therapy [(22.06±12.53) ng/L] compared with that in either before or healthy control group (both P<0.05). MMP-9 values were significantly higher in patients with hemorrhage after thrombolytic therapy (incidence rate was 26.5%, 9/34) compared with before treatment [(24.02±15.41) ng/L vs. (14.28±2.33) ng/L, P<0.05], and the values of MMP-9 were higher than those of patients without hemorrhage [(20.42±9.57) ng/L], but there was no statistically significant difference ( P >0.05). In patients with complete revascularization (revascularization rate was 58.8%, 20/34), MMP-9 level was markedly higher than before thrombolytic therapy after thrombolytic therapy [(19.26±7.94) ng/L vs. (13.63±3.02) ng/L, P<0.05], and the values of MMP-9 were higher than the no-revascularization patients [(18.97±4.23) ng/L], but there was no statistically significant difference ( P >0.05). CONCLUSION: Thrombolytic therapy activated MMP-9, and MMP-9 increased the risk of hemorrhage after thrombolytic therapy, and it participated in the mechanisms of hemorrhagic tendency after thrombolysis.

[Study of the protection and mechanism of IGF-1 on tau protein hyperphosphorylation in PC12 cells induced by Abeta(1-40)].

OBJECTIVE: To investigate the effect and the molecular mechanism of insulin-like growth factor 1 (IGF-1) on the level of tau protein phosphorylation in PC12 cells induced by aggregated beta-amyloid protein(1-40) (Abeta(1-40)). METHODS: MTT assay was used to measure the survival rate of PC12 cells, Western blot was applied to detect tau phosphorylation level, total tau, glycogen synthase kinase-3beta (GSK-3beta), and phosphorylation of GSK-3beta Ser9 for observing the effect of IGF-1 or LiCl, a specific inhibitor of GSK-3beta, on Abeta-induced tau protein phosphorylation in PC12 cells. RESULTS: Different concentrations of IGF-1 could improve the survival rate of PC12 cells compared with that of Abeta(1-40) group (P < 0.05), and the best protective effect was observed in 1 microg/mL IGF-1 group. The levels of tau protein phosphorylation in the sites of Ser396, Ser(199/202) and the amount of whole tau increased after 3 h exposure and reached the maximum level after 12 h exposure to Abeta(1-40), meanwhile, the expressions of the amount of whole GSK-3beta was also increased (P < 0.05), but a decreased phosphorylation of GSK-3betaSer9 was observed (P < 0.05). Pretreatment with several dose of IGF-1 or LiCl, markedly reduced Abeta(1-40)-induced tau hyperphosphorylation and the expression of GSK-3beta (P < 0.05), but the expression of phosphorylation of GSK-3betaSer9 was increased (P < 0.05). CONCLUSION: The levels of tau protein phosphorylation in the sites of Ser396, Ser(199/202) and the amount of whole tau increased by Abeta(1-40) in PC12 cells, GSK-3beta activation by Abeta(1-40) may lead to extensive tau phosphorylation. IGF-1 could attenuate Abeta(1-40)-induced tau protein hyperphosphorylation by inhibiting the activation of GSK-3beta.