Volume 5 • Issue 3 • 1000148
Autism Open Access
ISSN:2165-7890 AUO, an open access journal
Open Access Research Article
Autism - Open Access
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ISSN: 2165-7890
El Sayyad et al., Autism Open Access 2015, 5:3
http://dx.doi.org/10.4172/2165-7890.1000148
Keywords: Cerebral Hemisphere; Cerebellum; Brain Function;
Diabetes; Hypercholesterolemia; Fish Oil
Introduction
he prevalence of diabetes was markedly increased throughout the
world, reached approximately to 285 million, 90% of them possessing
type2 cases. In 2013, 381 million people had diabetes according to
International Diabetes Federation. he prevalence of the disease is
markedly progressed and the number being almost double by 2030
[1,2]. On the other hand, 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 lipid-
lowering drugs had abnormal cholesterol level [3-5]. Both diseases
are associated with the development of neurotoxicity and Alzheimer’s
disease (AD) [6].
Neurons required high glucose level for their high metabolic rate
and this depend on the extracellular level of glucose. Consequently,
hyperglycaemia was interfered with the brain function [7]. 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 inlammatory mediators such as interleukins IL-1β leading to the
development of the etiology of Parkinson’s disease (neurodegenerative
disease) [8].
In vitro studies of incubated murine Schwann cells (IMS32) with
30 and 56 mM glucose for 48 h and 7 and 14 days led to increase of
lipid peroxidation, aldose reductase level and caspase 3, the markers
of neuronal damage [9]. Diabetic rats was found to possess decreased
glucose levels associated with increased mitochondrial damage via
altering both cytochrome c and phosphatidylserine leading to DNA
damage [10]. It is known that the mitochondrial system is a main
source of cellular reactive oxygen species. he production of H2O2
is afected by the mitochondrial membrane potential and oxygen
consumption. Altered insulin secretion led to oxidative neuronal
damage and neurodegeneration [11]. Hyperglycemia was found to
cause mitochondrial fragmentation and production of reactive oxygen
species, the major complications associated with diabetes and obesity
[12,13]. It is well known that astrocyte is the main neurovascular unit
involved in brain strocke. Oxygen-glucose deprivation was found
to alter the expression/distribution and activity of glial glutamate
transporters, impaired and afect intracellular levels of glutathione
in diferentiated astrocytes [14]. Astrocytes are the main source of
apolipoprotein E (apoE) comparing with oligodendrocytes, microglia,
and ependymal cells which protect it against glutamate induce cell
damage and mediate cholesterol homeostasis in the brain, however
disrupted cholesterol metabolism led to overexpression ApoE mRNA
levels mediating the development of Alzheimer’s disease (AD) 15,16].
here are several factors involving in the development of AD include
*Corresponding author: Hassan IH El Sayyad, Faculty of Science, Mansoura
University, Mansoura, Egypt, Tel: 0020502254850, E-mail: elsayyad@mans.edu.eg
Received July 30, 2015; Accepted August 31, 2015; Published September 07,
2015
Citation: El Sayyad HIH, Bakr IHM, El Mansi AA, Amin AH, El Beeh ME, et al.
(2015) Fish Oil Supplementation Ameliorated Brain Lesions Induced by Diabetes
and Hypercholesterolemia in Male Wistar Albino Rats. Autism Open Access 5: 148.
doi:10.4172/2165-7890.1000148
Copyright: © 2015 El Sayyad HIH, et al. This is an open-access article distributed
under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the
original author and source are credited.
Fish Oil Supplementation Ameliorated Brain Lesions Induced by Diabetes
and Hypercholesterolemia in Male Wistar Albino Rats
Hassan IH El Sayyad
1
*, Iman HM Bakr
1
, Ahmed A El Mansi
1
, Ali H amin
1,2
, Mohamed E El Beeh
1,2
, Adel MA Asiri
2
1
Zoology Department, Faculty of Science, Mansoura University, Egypt
2
Institiute of Scientiic Research and Revival of Islamic Heritage, Um Al-Qura University, Mecca, kingdom Saudi Arabia
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), ish oil-treatment, hypercholesterolemic
group (H), hypercholesterolemic & ish oil-treatment (HF), diabetic- group (D), diabetic and ish oil-treatment (DF),
combined hypercholesterolemic and diabetic group (HD) and combined hypercholesterolemic and diabetic group
and ish-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, Sigma-
aldrich, 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
inding 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 iniltration 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 ish 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.