Sulforhodamine 101 (SR101) has been extensively used for investigation as a specific marker for astroglia in vivo and activity-dependent dye for monitoring regulated exocytosis. Here, we report that SR101 has bioactive effects on neuronal activity. Perfusion of slices with SR101 (1 μM) for 10 min induced long-term potentiation of intrinsic neuronal excitability (LTP-IE) and a long-lasting increase in evoked EPSCs (eEPSCs) in CA1 pyramidal neurons in hippocampal slices. The increase in intrinsic neuronal excitability was a result of negative shifts in the action potential (AP) threshold. The N-methyl D-aspartate receptor (NMDAR) antagonist, AP-5 (50 μM), blocked SR101-induced LTP-IE, but glutamate receptor blockers, AP-5 (50 μM), MCPG (200 μM), and MSOP (100 μM), only partially blocked SR101-induced potentiation of eEPSCs. SR101 induced an enhancement of evoked synaptic NMDAR currents, suggesting that SR101 enhances activation of synaptic NMDARs. SR101-induced LTP-IE and potentiation of synaptic transmission triggered spontaneous neuronal firing in slices and in vivo epileptic seizures. Our results suggest that SR101 is an epileptogenic agent that long-lastingly lowers the AP threshold to increase intrinsic neuronal excitability and enhances the synaptic efficacy to increase synaptic inputs. As such, SR101 can be used as an experimental tool to induce epileptic seizures.

Hyper-Hcy and low serum folate levels were associated with an increased risk of AMVT. The homozygous (TT) genotype of MTHFR gene mutation may be a crucial hereditary risk factor in the development of AMVT for a Chinese population.

High glucose plays an important role in the pathogenesis of atherosclerosis. In this study, we assessed the effects of high glucose on human umbilical vein endothelial cell (HUVEC) apoptosis. Additionally, we investigated whether alpha-lipoic acid, an antioxidant, prevents high glucose-induced apoptosis of HUVECs. HUVECs were treated with high glucose in the presence or absence of alpha-lipoic acid. Treatment of HUVECs with high glucose changed cell morphology and induced DNA fragmentation, leading to apoptosis. Apoptosis was induced by high glucose in a dose-and time-dependent fashion. High glucose markedly elevated Bax, and decreased NF-kappaB and Bcl-2 expression. Most importantly, pretreatment with alpha-lipoic acid protected against high glucose-induced apoptosis in the endothelial cells. alpha-Lipoic acid significantly promoted the expression of NF-kappaB while decreasing the expression of Bax and the activities of caspase-3 and-9 without significantly affecting the Bcl-2 level. Our data suggest that high glucose induces apoptosis in endothelial cells. alpha-Lipoic acid effectively attenuates high glucose-induced endothelial cell apoptosis. These findings provide new perspectives on the role of alpha-lipoic acid in cardiovascular disease.

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