Nathani Minaz1, Rema Razdan1, Bruce D Hammock2, Sumanta Kumar Goswami3. 1. Department of Pharmacology, Al-Ameen College of Pharmacy, Bangalore, Karnataka, India. 2. Department of Entomology and Nematology, and Comprehensive Cancer Center, University of California, Davis, CA, USA. 3. Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, USA. Electronic address: skg74@drexel.edu.
Abstract
BACKGROUND: Pharmacological inhibition of soluble epoxide hydrolase (sEH) enhances the synaptic function in the CNS and has a protective role in cognitive decline. We hypothesized that the sEH inhibitor TPPU might prevent the diabetes-induced decline in learning and memory which is associated with an alteration in the level of neurotransmitters and oxidative stress. METHODS: Type 1 diabetes was induced in rats and the animals were treated with TPPU for 8 weeks. The learning and memory functions were assessed by the Barnes maze and a step-down test. Indicators of oxidative stress, levels of neurotransmitters, and activity of acetylcholinesterase were measured in the discrete regions of the brain. RESULTS: Our results revealed that treatment with TPPU significantly improves learning and memory performance in diabetic rats along with decreasing the level of blood sugar. Moreover, treatment with TPPU significantly prevented the diabetes-induced alteration in levels of neurotransmitters, the activity of acetylcholinesterase and preserved anti-oxidant defence system. CONCLUSION: Inhibition of the sEH alleviates diabetes-induced decline in learning and memory.
BACKGROUND: Pharmacological inhibition of soluble epoxide hydrolase(sEH) enhances the synaptic function in the CNS and has a protective role in cognitive decline. We hypothesized that the sEH inhibitor TPPU might prevent the diabetes-induced decline in learning and memory which is associated with an alteration in the level of neurotransmitters and oxidative stress. METHODS: Type 1 diabetes was induced in rats and the animals were treated with TPPU for 8 weeks. The learning and memory functions were assessed by the Barnes maze and a step-down test. Indicators of oxidative stress, levels of neurotransmitters, and activity of acetylcholinesterase were measured in the discrete regions of the brain. RESULTS: Our results revealed that treatment with TPPU significantly improves learning and memory performance in diabeticrats along with decreasing the level of blood sugar. Moreover, treatment with TPPU significantly prevented the diabetes-induced alteration in levels of neurotransmitters, the activity of acetylcholinesterase and preserved anti-oxidant defence system. CONCLUSION: Inhibition of the sEH alleviates diabetes-induced decline in learning and memory.
Authors: Frances M Potjewyd; Joel K Annor-Gyamfi; Jeffrey Aubé; Shaoyou Chu; Ivie L Conlon; Kevin J Frankowski; Shiva K R Guduru; Brian P Hardy; Megan D Hopkins; Chizuru Kinoshita; Dmitri B Kireev; Emily R Mason; Charles T Moerk; Felix Nwogbo; Kenneth H Pearce; Timothy I Richardson; David A Rogers; Disha M Soni; Michael Stashko; Xiaodong Wang; Carrow Wells; Timothy M Willson; Stephen V Frye; Jessica E Young; Alison D Axtman Journal: Alzheimers Dement (N Y) Date: 2022-04-12