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Neuron. 2004 Sep 2;43(5):633-45.

Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model.

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1
Department of Medicine, University of California, Los Angeles, 90095, USA.

Abstract

Learning and memory depend on dendritic spine actin assembly and docosahexaenoic acid (DHA), an essential n-3 (omega-3) polyunsaturated fatty acid (PFA). High DHA consumption is associated with reduced Alzheimer's disease (AD) risk, yet mechanisms and therapeutic potential remain elusive. Here, we report that reduction of dietary n-3 PFA in an AD mouse model resulted in 80%-90% losses of the p85alpha subunit of phosphatidylinositol 3-kinase and the postsynaptic actin-regulating protein drebrin, as in AD brain. The loss of postsynaptic proteins was associated with increased oxidation, without concomitant neuron or presynaptic protein loss. n-3 PFA depletion increased caspase-cleaved actin, which was localized in dendrites ultrastructurally. Treatment of n-3 PFA-restricted mice with DHA protected against these effects and behavioral deficits and increased antiapoptotic BAD phosphorylation. Since n-3 PFAs are essential for p85-mediated CNS insulin signaling and selective protection of postsynaptic proteins, these findings have implications for neurodegenerative diseases where synaptic loss is critical, especially AD.

PMID:
15339646
PMCID:
PMC2442162
DOI:
10.1016/j.neuron.2004.08.013
[Indexed for MEDLINE]
Free PMC Article

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