Inhibitor of Soluble Epoxide Hydrolase Attenuates Decline in Learning and Memory of Diabetic Rats

Abstract

Epoxyeicosatrienoic acids (EETs) are epoxide derivatives formed from arachidonic acid and are neuroprotectant. These bioactive lipids are degraded by soluble epoxide hydrolase (sEH). Pharmacological inhibition of sEH enhances the synaptic function in the central nervous system and has a protective role in the age‐related cognitive decline. We have evaluated the hypothesis that the sEH inhibitor TPPU might prevent a diabetes‐induced decline in learning and memory which is associated with alteration in the level of neurotransmitter and oxidative stress. Type 1 diabetes (streptozotocin 52 mg/kg, i.p.) was induced in rats and the animals were treated with TPPU (0.1 and 0.3 mg/kg body weight; p.o.) for 8 weeks. The learning and memory functions were assessed by Barnes maze and step down test. Level of oxidative stress indicators (reduced glutathione and malondialdehyde) and neurotransmitters (γ‐Aminobutyric acid, norepinephrine, and dopamine), and activity of acetylcholinesterase and were measured in the discrete regions of the brain. Our results revealed that treatment with TPPU which penetrates the blood‐brain barrier significantly improved learning and memory performance in diabetic rats with a parallel decrease in the level of blood sugar. Moreover, treatment with TPPU significantly minimized the diabetes‐induced alteration in levels of neurotransmitters and activity of acetylcholinesterase. In addition, TPPU protected anti‐oxidant defense system. Based on our experimental findings, it can be concluded that the inhibition of sEH is a viable strategy for retrieving diabetes‐induced decline in learning and memory.Support or Funding InformationThis study was partially funded by the National Institute of Environmental Health Sciences (NIEHS) [Grant R01 ES002710], NIEHS Superfund Research Program [Grant P42 ES004699], West Coast Central Comprehensive Metabolomics Center [Grant U24 DK097154] to BDH.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.