gamma-linolenic-acid and Alzheimer-Disease

The role of fish oil, primrose oil and their mixture in ameliorating the changes in Alzheimer's like model was evaluated in rats. Primrose oil and primrose/fish oil mixture fatty acids composition was assessed by gas chromatography. The rat experiment consisted of 5 groups; the first fed on balanced diet as control normal (CN); the other four groups treated with intraperitoneal aluminum lactate and consumed dyslipidemic diet; one group served as control Alzheimer's like disease (CA) while the other three groups (test groups) received daily oral dose from primrose oil, fish oil and primrose/fish oil mixture separately for 5 weeks. Results showed primrose oil and primrose/ fish oil mixture to contain gamma linolenic acid as 9.15 and 4.3% of total fatty acids, respectively. Eicosapentaenoic and docosahexaenoic were present as 10.9 and 6.5 %, respectively in the oil mixture. Dyslipidemia and increased erythrocyte sedimentation rate (ESR), plasma butyrylcholinesterase (BChE), brain malondialdehyde (MDA) and NO with decrease in plasma magnesium, brain catalase, reduced glutathione, body weight gain and brain weight were demonstrated in CA compared to CN. Brain histopathology and immuno-histochemistry showed neuronal degeneration and neurofibrillary tangles with elevated myeloperoxidase and nuclear factor-kappa B in CA compared to CN. The tested oils demonstrated neuro-protection reflected in the variable significant improvement of biochemical parameters, immuno-histochemistry and brain histopathology. Primrose/fish oil mixture was superior in reducing ESR, brain MDA, plasma activity of BChE and brain histopathological changes along with elevating plasma magnesium. Primrose/fish oil mixture and fish oil were more promising in improving plasma high density lipoprotein cholesterol (HDL-C) than primrose. Fish oil was the most efficient in improving plasma total cholesterol (T-C), low density lipoprotein cholesterol and T-C /HDL-C. Primrose/fish oil mixture and primrose oil were superior in elevating brain catalase compared to fish oil. Other parameters were equally improved by the different oil treatments. Primrose oil, fish oil and their mixture reduced the progression of Alzheimer's disease in rats with superiority to primrose/fish oil mixture.

Topics: Aluminum Compounds; Alzheimer Disease; Animals; Brain; Butyrylcholinesterase; Catalase; Cholesterol; Disease Models, Animal; Disease Progression; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fish Oils; gamma-Linolenic Acid; Lactates; Male; Malondialdehyde; Plant Oils; Primula; Rats; Rats, Inbred Strains

Polyunsaturated fatty acids (PUFAs) are closely related to various physiological conditions. In several age-related diseases including Alzheimer's disease (AD) altered PUFAs metabolism has been reported. However, the mechanism behind PUFAs impairment and AD developpement remains unclear. In humans, PUFAs biosynthesis requires delta-5 desaturase (D5D), delta-6 desaturase (D6D) and elongase 2 activities; which are encoded by fatty acid desaturase 1 (FADS1), fatty acid desaturase 2 (FADS2), and elongation of very-long-chain fatty acids-like 2 (ELOVL2) genes, respectively. In the present work, we aim to assess whether genetic variants in FADS1, FADS2 and ELOVL2 genes influence plasma and erythrocyte PUFA composition and AD risk. A case-control study was carried out in 113 AD patients and 161 healthy controls.Rs174556, rs174617, and rs3756963 of FADS1, FADS2, and ELOVL2 genes, respectively were genotyped using PCR-RFLP. PUFA levels were quantified using Gas Chromatography. Genotype distributions of rs174556 (FADS1) and rs3756963 (ELOVL2) were different between case and control groups. The genotype TT of rs174556 and rs3756963 single nucleotide polymorphism (SNP) increases significantly the risk of AD in our population. PUFA analysis showed higher plasma and erythrocyte arachidonic acid (AA) level in patients with AD, whereas only plasma docosahexaenoic acid (DHA) was significantly decreased in AD patients. The indexes AA/Dihomo-gamma-linolenic acid (DGLA) and C24:4n-6/Adrenic acid (AdA) were both higher in the AD group. Interestingly, patients with TT genotype of rs174556 presented higher AA level and AA/DGLA index in both plasma and erythrocyte. In addition, higher AA and AA/DGLA index were observed in erythrocyte of TT genotype ofrs3756963 carrier's patients. Along with, positive correlation between AA/DGLA index, age or Gamma-linolenic acid (GLA)/ Linoleic acid (LA) index was seen in erythrocyte and /or plasma of AD patients. After adjustment for confounding factors, the genotype TT of rs174556, erythrocyte AA and AA/DGLA index were found to be predictive risk factors for AD while plasma DHA was found associated with lower AD risk. Both rs174556 and rs3756963 influence AD risk in the Tunisian population and they are likely associated with high AA level. The combination of the two variants increases further the susceptibility to AD. We suggest that FADS1 and ELOVL2 variants could likely regulate the efficiency of AA biosynthesis which could be at the origin

Topics: 8,11,14-Eicosatrienoic Acid; Alleles; Alzheimer Disease; Arachidonic Acid; Case-Control Studies; Chromatography, Gas; Delta-5 Fatty Acid Desaturase; Docosahexaenoic Acids; Erythrocytes; Fatty Acid Desaturases; Fatty Acid Elongases; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Genotype; Humans; Linoleic Acid; Polymorphism, Single Nucleotide; Regression Analysis; Risk Factors; Tunisia