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PMID: 15339646 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Neuron ·Vol. 43 ·No. 5 ·2004-09-02 ·Pages 633-45

Calon F, Lim GP, Yang F, Morihara T, Teter B, Ubeda O, Rostaing P, Triller A, Salem N, Ashe KH, Frautschy SA, Cole GM

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.

MeSH Terms
Actins/metabolism Alzheimer Disease/metabolism,pathology,prevention & control Animals Apoptosis/drug effects,genetics Brain/drug effects,metabolism,pathology Carrier Proteins/drug effects,metabolism Dendrites/drug effects,metabolism,pathology Dietary Fats, Unsaturated/metabolism,pharmacology Disease Models, Animal Docosahexaenoic Acids/metabolism,pharmacology,therapeutic use Down-Regulation/genetics Female Food, Formulated Humans Male Mice Mice, Transgenic Microscopy, Electron Nerve Tissue Proteins/metabolism Neuropeptides/metabolism Oxidative Stress/drug effects,genetics Phosphatidylinositol 3-Kinases/metabolism Phosphorylation/drug effects Protein Subunits/metabolism Synapses/drug effects,metabolism,pathology bcl-Associated Death Protein
Chemicals
Actins BAD protein, human Bad protein, mouse Carrier Proteins Dietary Fats, Unsaturated Nerve Tissue Proteins Neuropeptides Protein Subunits bcl-Associated Death Protein drebrins Docosahexaenoic Acids Phosphatidylinositol 3-Kinases
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Calon Frédéric
Department of Medicine, University of California, Los Angeles, 90095, USA.
Lim Giselle P
Yang Fusheng
Morihara Takashi
Teter Bruce
Ubeda Oliver
Rostaing Phillippe
Triller Antoine
Salem Norman
Ashe Karen H
Frautschy Sally A
Cole Greg M
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Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
0896-6273
DOI
10.1016/j.neuron.2004.08.013
Published
2004-09-02
Pages
633-45
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC2442162
Subset
IM
Grants
NIA NIH HHS · AG10685 · United States
NIA NIH HHS · P50 AG005142 · United States
NINDS NIH HHS · R01 NS043946 · United States
NIA NIH HHS · R01 AG13741 · United States
NIA NIH HHS · P01 AG16570 · United States
NIA NIH HHS · P50 AG05142 · United States
NIA NIH HHS · AG16793 · United States
NIA NIH HHS · P50 AG 16570 · United States
NIA NIH HHS · R01 AG016793 · United States
NIA NIH HHS · R01 AG013741 · United States
NIA NIH HHS · P50 AG016570 · United States
NINDS NIH HHS · NS43946 · United States
NIA NIH HHS · R01 AG010685 · United States
Corrections
CommentIn
PMID: 15339638
External Links
PubMed source DOI: 10.1016/j.neuron.2004.08.013 PMC Full Text View journal details
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