Blockade of voltage-gated potassium channels ameliorates diabetes-associated cognitive dysfunction in vivo and in vitro.

Blockade of voltage-gated potassium channels ameliorates diabetes-associated cognitive dysfunction in vivo and in vitro. Exp Neurol. 2019 Jun 26;:112988 Authors: Yan W, Zhang M, Yu Y, Yi X, Guo T, Hu H, Sun Q, Chen M, Xiong H, Chen L Abstract The voltage-gated potassium (Kv) channel blockers tetraethylammonium (TEA) and 4-aminopyridine (4-AP) have shown beneficial effects on some neurological disorders. But their involvements in diabetes-associated cognitive dysfunction are still unknown. The present study aims to investigate whether the blockade of Kv channels by TEA and 4-AP alleviate cognitive decline in diabetes. In vivo, the effects of TEA and 4-AP (5 mg/kg body weight per day, 1 mg/kg body weight per day intraperitoneal injected for 4 weeks, respectively) were investigated in streptozotocin-induced C57BL/6 diabetic mice. In vitro study, we investigated the effects of TEA and 4-AP on the high glucose (HG) -stimulated primary cortical neurons. The results showed that TEA and 4-AP ameliorated the cognitive decline of diabetic mice in the Morris water maze test; improved the ultrastructure of pancreatic β cells, hippocampal neurons and synapses, decreased oxidative stress, modulated apoptosis-related proteins, and activated phosphatidylinositol 3-kinase (PI3K)/ Protein kinase-B (PKB or Akt) signaling pathway. In the HG-stimulated primary cultured cortical neurons, TEA and 4-AP increased the cell viability, decreased oxidativ...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research