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DOCOSAHEXAENOIC ACID-INDUCED PROTECTIVE EFFECT AGAINST IMPAIRED LEARNING IN AMYLOID β-INFUSED RATS IS ASSOCIATED WITH INCREASED SYNAPTOSOMAL MEMBRANE FLUIDITY

Authors


Michio Hashimoto, Department of Environmental Physiology; Shimane University Faculty of Medicine, Izumo 693-8501, Japan. Email: michio1@med.shimane-u.ac.jp

SUMMARY

  • 1In the present study, we investigated the relationship between the docosahexaenoic acid (DHA)-induced protection of learning deficit of amyloid β(1−40)-infused Alzheimer's disease (AD) model rats and changes in synaptosomal plasma membrane fluidity of the cerebral cortex.
  • 2Synaptosomal membrane lateral and rotational fluidity were measured using pyrene excimer spectroscopy and fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH), respectively.
  • 3Avoidance learning ability, as assessed by a two-way active avoidance paradigm, decreased significantly in the AD model rats.
  • 4Pyrene-determined annular/non-annular fluidity ratio and the DPH-determined bulk fluidity of the synaptosomal plasma membrane decreased in the amyloid β(1−40)-infused rats. Oral pre-administration of DHA (300 mg/kg per day for 12 weeks) significantly increased both lateral and rotational fluidity.
  • 5The synaptosomal membrane DHA content increased and the cholesterol to phospholipid molar ratio and lipid peroxidation decreased.
  • 6The annular to non-annular fluidity ratio of the synaptic plasma membrane was positively correlated with total avoidance learning.
  • 7The present results indicate that DHA-induced alterations in synaptic plasma membrane fluidity may contribute to the synaptic plasma membrane-related functions that constitute avoidance learning-related memory in amyloid β(1−40)-infused rats.

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