Abstract

Diabetes and hypercholesterolemia are dyslipidemic diseases and have certain role in brain dysfunction, but little of works are concerning with it. In the present study we used eighty male Wistar rats weighing approximately 100 ±15 gram. The animals were arranged into 8 groups; Control (C), fish oil-treatment, hypercholesterolemic group (H), hypercholesterolemic & fish oil-treatment (HF), diabetic- group (D), diabetic and fish oil-treatment (DF), combined hypercholesterolemic and diabetic group (HD) and combined hypercholesterolemic and diabetic group and fish-oil-treatment (HDF). Diabetes was induced by streptozotocin (40mg/kg single dose in citrate buffer pH4.6). Hypercholesterolemia was carried out by feeding rats on diet containin3% cholesterol. Fish oil (Menhaden, Sigmaaldrich, highest purity) was supplemented orally every other day at 100mg/kg body weight. Treatment was carried out for 16 weeks. At the end of treatment, brain tissues were subjected for histological investigation and biochemical assessments of dopamine, serotonin, vascular endothelial growth factor, 8-deoxyhydroxy-guanosine, adhesion molecules and phospholipids beside histological investigation of cerebral hemisphere and cerebellum. The present finding revealed marked depletion of the assayed neurotransmitters and phospholipids and increased of vascular endothelial growth factor, adhesion molecules and 8-deoxy hydroxy-guanosine. Histological observations of cerebral hemisphere revealed widespread of hemorrhagic spots in hypercholesterolemia, neovascualarization in combined diabetes and hypercholesterolemia and dense lymphocytic infiltration in diabetic group. All the experimental groups possessed edematous lesions in the inner plexiform layer. Cerebellar cortex exhibited massive degeneration of Purkinje cells and granular cell layer in diabetic and or hypercholesterolemia. Fish oil supplementation improved the brain function and histological picture. The authors concluded that fish oil contain short and long chain omega-3 fatty acids fatty acid which support the brain function and scavenge the free radicals damaging brain cells.

Highlights

  • The prevalence of diabetes was markedly increased throughout the world, reached approximately to 285 million, 90% of them possessing type2 cases

  • Fish oil supplementation restored the level of both assayed neurotransmitters and adhesion molecules but attain the normal levels

  • Concerning intracellular and vascular adhesion molecules (ICAM-1& VCAM-1), Vascular endothelial growth factor (VEGF) and 8-HDG, their levels were markedly increased in brain tissues of diabetes and or hypercholesterolemia and ameliorated after fish oil supplementation but still not matched with the control values

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Summary

Introduction

The prevalence of diabetes was markedly increased throughout the world, reached approximately to 285 million, 90% of them possessing type cases. Hypercholesterolemia and obesity were associated with 50% of the mortality caused by ischemic heart disease and stroke, and reached almost from 3% to 53% in men, and from 4% to 40% in women as well as over 50% of men and women taking lipidlowering drugs had abnormal cholesterol level [3,4,5]. Both diseases are associated with the development of neurotoxicity and Alzheimer’s disease (AD) [6]. Type 2 diabetes model ob/ob mice was found to exhibit impaired insulin expression in pancreas, liver and midbrain as well as over-expressed α-synuclein and endoplasmic reticulum stress markers (CHOP and GRP78) in pancreas and midbrain, followed by increased production of inflammatory mediators such as interleukins IL-1β leading to the development of the etiology of Parkinson’s disease (neurodegenerative disease) [8]

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