Docosahexaenoic acid-induced amelioration on impairment of memory learning in amyloid beta-infused rats relates to the decreases of amyloid beta and cholesterol levels in detergent-insoluble membrane fractions.

We investigated the effects of dietary administration of docosahexaenoic acid (DHA; C22:6n-3) on the levels of amyloid beta (A beta) peptide (1-40) and cholesterol in the nonionic detergent Triton 100 x-insoluble membrane fractions (DIFs) of the cerebral cortex and, also, on learning-related memory in an animal model of Alzheimer's disease (AD) rats infused with A beta peptide (1-40) into the cerebral ventricle. The infusion increased the levels of A beta peptide and cholesterol in the DIFs concurrently with a significant increase in reference memory errors (measured by eight-arm radial-maze tasks) compared with those of vehicle rats. Conversely, the dietary administration of DHA to AD-model rats decreased the levels of A beta peptide and cholesterol in the DIFs, with the decrease being more prominent in the DHA-administered rats. Regression analysis revealed a significant positive correlation between A beta peptide and each of cholesterol, palmitic acid and stearic acid, and between the number of reference memory errors and each of cholesterol, palmitic, stearic and oleic acid; moreover, a significant negative correlation was observed between the number of reference memory errors and the molar ratio of DHA to palmitic plus stearic acid. These results suggest that DHA-induced protection of memory deficits in AD-model rats is related to the interactions of cholesterol, palmitic acid or stearic acid with A beta peptides in DIFs where DHA ameliorates these interactions.
AuthorsMichio Hashimoto, Shahdat Hossain, Haqu Agdul, Osamu Shido
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 1738 Issue 1-3 Pg. 91-8 (Dec 30 2005) ISSN: 0006-3002 [Print] Netherlands
PMID16427803 (Publication Type: Journal Article)
Chemical References
  • Amyloid beta-Peptides
  • Detergents
  • Fatty Acids
  • Docosahexaenoic Acids
  • Octoxynol
  • Cholesterol
  • Alzheimer Disease (drug therapy)
  • Amyloid beta-Peptides (drug effects, metabolism, pharmacology)
  • Animals
  • Body Weight (drug effects)
  • Cell Membrane (chemistry, drug effects, metabolism)
  • Cerebral Cortex (drug effects)
  • Cholesterol (metabolism)
  • Detergents (pharmacology)
  • Disease Models, Animal
  • Docosahexaenoic Acids (pharmacology)
  • Fatty Acids (metabolism)
  • Infusions, Intralesional
  • Learning (drug effects)
  • Memory (drug effects)
  • Octoxynol (pharmacology)
  • Rats
  • Rats, Wistar
  • Regression Analysis
  • Solubility

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