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

1 In 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. 2 Synaptosomal membrane lateral and rotational fluidity were measured using pyrene excimer spectroscopy and fluorescence polarization of 1,6‐diphenyl‐1,3,5‐hexatriene (DPH), respectively. 3 Avoidance learning ability, as assessed by a two‐way active avoidance paradigm, decreased significantly in the AD model rats. 4 Pyrene‐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. 5 The synaptosomal membrane DHA content increased and the cholesterol to phospholipid molar ratio and lipid peroxidation decreased. 6 The annular to non‐annular fluidity ratio of the synaptic plasma membrane was positively correlated with total avoidance learning. 7 The 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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