Neuroprotective effect of polysaccharide separated from Perilla frutescens Britton var. acuta Kudo against H2O2-induced oxidative stress in HT22 hippocampus cells

This study was carried out to evaluate the neuroprotective activity of polysaccharide extracts isolated from Perilla frutescens (PEPF) in H₂O₂-treated HT22 hippocampus cells. The PEPF treatment was found to increase the anti-oxidant activities of HT22 hippocampus cells. PEPF treatment resulted in a significant protection of HT22 hippocampus cells against H₂O₂-induced neurotoxicity, this protection ultimately occurred through an inhibition of ROS-mediated intracellular Ca²⁺ levels leading to MAPKs and NF-κB, as well as the accumulation of PI3K/AKT and Nrf2-mediated HO-1/NQO1 pathways. Furthermore, PEPF not only decreased the expression of Bax, cytochrome c, and cleaved caspases-3, -8, and -9, but also increased the expression of PARP and Bcl-2 in the H₂O₂-treated HT22 hippocampus cells, which overall contributed to the neuroprotective action. PEPF retains its mitochondrial membrane potential and reduces the elevated levels of sub-G1 phase and apoptotic morphological features induced by H₂O₂. It also reduces the malondialdehyde levels and enhances the intracellular SOD activity.     

Epigenetic control of early neurodegenerative events in diabetic retinopathy by the histone deacetylase SIRT6

Diabetic retinopathy (DR ) is one of the common complications associated with diabetes mellitus and the leading cause of blindness worldwide. Recent research has demonstrated that DR is not only a microvascular disease but may be a result of neurodegenerative processes. Moreover, glucose‐induced neuron and glial cell damage may occur shortly after the onset of diabetes which makes the disease hard to diagnose at early stages. SIRT 6, a NAD ‐dependent sirtuin deacylase, modulates aging, energy metabolism, and neurodegeneration. In previous studies we showed that SIRT 6 deficiency causes major retinal transmission defects, changes in the expression of glycolytic genes, and elevated levels of apoptosis. Given the importance of glucose availability for retinal function and the critical role of SIRT 6 in modulating glycolysis, we aimed to analyze SIRT 6 participation in the molecular machinery that regulates the development of experimental DR . Using non‐obese diabetic mice, we determined by western blot that 2 weeks after the onset of the disease, high glucose concentrations induced retinal increase in a neovascularization promoting factor (vascular endothelial growth factor, VEGF ), and the loss of a neuroprotective factor (brain‐derived neurotrophic factor, BDNF) associated with reduced levels of SIRT 6 and increased acetylation levels of its substrates (H3K9 and H3K56) suggesting a deregulation of key neural factors. Noteworthy, retinas from CNS conditionally deleted SIRT 6 mice showed a resemblance to diabetic retinas exhibiting lower protein levels of BDNF factor and increased protein levels of VEGF . Moreover, cultured Müller glial cells subjected to high glucose concentrations exhibited decreased levels of SIRT 6 and increased levels of H3K56 acetylation. In addition, the increment of VEGF levels induced by high glucose was reverted by the over‐expression of SIRT 6 in this cell type. Accordingly, siRNA experiments showed that, when SIRT 6 was silenced, VEGF levels increased. Our findings suggest that epigenetically regulated neurodegenerative events may occur at an early diabetic stage prior to the characteristic proliferative and vascular changes observed at a later diabetic stage.

     

瘦素对小鼠脑缺血/再灌注损伤神经元凋亡的影响

目的：研究Leptin在脑缺血性损伤神经元凋亡中的作用及其机制。方法：将75只雄性昆明小鼠完全随机分成3组,即假手术组、缺血/再灌注模型组、Leptin干预组;通过大脑中动脉栓塞（MCAO）复制小鼠局灶性脑缺血再灌注损伤模型,Leptin干预组在缺血0 min腹腔注射Leptin（1μg/g体重）,TUNEL染色检测神经元凋亡,RT-PCR检测凋亡相关基因bcl-2和caspase-3 mRNA表达,免疫组化凋亡相关基因bcl-2和caspase-3蛋白水平的表达。结果：模型组脑缺血中心区神经元以坏死为主,与假手术组相比,其半影区神经元凋亡数量显著增多、促凋亡基因cas-pase-3和抑凋亡基因bcl-2的mRNA和蛋白表达水平均显著升高（P<0.01）;与模型组比较,Leptin干预组半影区凋亡神经元数量显著减少、caspase-3 mRNA和蛋白表达水平显著降低（P<0.01）,抑凋亡基因bcl-2 mRNA和蛋白表达水平显著升高（P<0.01）。结论：Leptin能够通过上调抑凋亡基因bcl-2表达,下调促凋亡基因caspase-3表达抑制神经元凋亡,在脑缺血性损伤中发挥神经保护作用。