Donepezil improves neuropathy through activation of AMPK signalling pathwayin streptozotocin-induced diabetic mice.

In this study, streptozotocin (45 mg/kg for 5 Day, i.p.) was used to induce experimental DN. After confirmation of development of neuropathy, mice were randomly distributed into five groups: Group 1; negative control group received saline (0.9%NaCl), Group 2; diabetic mice received saline, Group (3-5); diabetic mice received daily donepezil (1, 2 or 4 mg/kg, p.o.) respectively for 20 days. Mice were then sacrificed under anesthesia then their sciatic nerve and spinal cord were dissected out and processed for biochemical and histopathological studies. Diabetic mice revealed severe histological abnormalities including degenerated neurons in the spinal cord and swollen myelin sheath with inflammatory edema observed in sciatic nerves. In addition, diabetic mice showed reduced expression of p-AMPK in sciatic nerves with consequent activation of AKT/MAPK/4EBP1. A significant upregulation of the N-Methyl-D-aspartate (NMDA) receptors in both cervical and lumbar regions of spinal cord of diabetic mice was also demonstrated. Donepezil, an AMPK activator, blocked the phosphorylation of AKT/MAPK/4EBP1, down regulate the expression of NMDA receptors and reversed hyperalagesia developed in diabetic mice. Therefore, Donepezil could be a potential pharmacological agent for management of DN. PMID: 30414938 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research