Docosahexaenoic Acid Protects from Dendritic Pathology in an Alzheimer's Disease

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Docosahexaenoic Acid Protects from Dendritic Pathology in an

Alzheimer's Disease Mouse Model

Frédéric Calon,1,3,7 Giselle P. Lim,1,3 Fusheng Yang,1,3 Takashi

Morihara,1,3 Bruce Teter,1,3 Oliver Ubeda,1,3 Phillippe Rostaing,4

Antoine Triller,4 Norman SalemJr. ,5 Karen H. Ashe,6 Sally A.

Frautschy,1,2,3 and Greg M. Cole1,2,3

 

1Department of Medicine, University of California, Los Angeles, Los

Angeles, CA 90095 USA

2Department of Neurology, University of California, Los Angeles, Los

Angeles, CA 90095 USA

3Greater Los Angeles Veterans Affairs Healthcare System, Geriatric

Research, Education and Clinical Center, Sepulveda, CA 91343 USA

4Laboratoire de Biologie Cellulaire de la Synapse Normale et

Pathologique, Institut National de la Santé et de la Recherche

Médicale U497, Ecole Normale Supérieure, 75005 Paris, France

5Section of Nutritional Neuroscience, Laboratory of Membrane

Biochemistry and Biophysics, Division of Intramural Clinical and

Biological Research, National Institute on Alcohol Abuse and

Alcoholism, National Institutes of Health, Rockville, MD 20852 USA

6Departments of Neurology and Neuroscience, University of Minnesota,

Minneapolis, MN 55455 USA

Correspondence:

Greg M. Cole

(818) 891-7711 ext. 9949 (phone)

(818) 895-5835 (fax)

gmcole

 

 

 

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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 p85 & #945;

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.

 

 

Footnotes

7Present address: Molecular Endocrinology and Oncology Research

Center, Laval University Medical Center (CHUL), Québec, Qc, G1V 4G2,

and Faculty of Pharmacy, Laval University, Québec, Qc, G1K 7P4, Canada.

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* Food for Thought: Essential Fatty Acid Protects against Neuronal

Deficits in Transgenic Mouse Model of AD

Lennart Mucke and Robert E. Pitas

Neuron, 2004, 43:5:596-599

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