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

Frédéric Calon, Giselle P. Lim, Fusheng Yang, Takashi Morihara, Bruce Teter, Oliver Ubeda, Phillippe Rostaing, Antoine Triller, Norman Salem, Karen H Ashe, Sally A. Frautschy, Greg M. Cole

Research output: Contribution to journalArticle

561 Citations (Scopus)

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 p85α 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.

Original languageEnglish (US)
Pages (from-to)633-645
Number of pages13
JournalNeuron
Volume43
Issue number5
DOIs
StatePublished - Sep 2 2004

Fingerprint

Docosahexaenoic Acids
Omega-3 Fatty Acids
Alzheimer Disease
Pathology
Actins
Proteins
Phosphatidylinositol 3-Kinase
Dendritic Spines
Caspases
Dendrites
Unsaturated Fatty Acids
Neurodegenerative Diseases
Phosphorylation
Learning
Insulin
Neurons
Brain
Therapeutics

Cite this

Calon, F., Lim, G. P., Yang, F., Morihara, T., Teter, B., Ubeda, O., ... Cole, G. M. (2004). Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model. Neuron, 43(5), 633-645. https://doi.org/10.1016/j.neuron.2004.08.013

Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model. / Calon, Frédéric; 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.

In: Neuron, Vol. 43, No. 5, 02.09.2004, p. 633-645.

Research output: Contribution to journalArticle

Calon, F, Lim, GP, Yang, F, Morihara, T, Teter, B, Ubeda, O, Rostaing, P, Triller, A, Salem, N, Ashe, KH, Frautschy, SA & Cole, GM 2004, 'Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model', Neuron, vol. 43, no. 5, pp. 633-645. https://doi.org/10.1016/j.neuron.2004.08.013
Calon, Frédéric ; 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. / Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model. In: Neuron. 2004 ; Vol. 43, No. 5. pp. 633-645.
@article{cc9e38ea92a44c41b9d4f70de8b3c447,
title = "Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model",
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 p85α 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.",
author = "Fr{\'e}d{\'e}ric Calon and Lim, {Giselle P.} and Fusheng Yang and Takashi Morihara and Bruce Teter and Oliver Ubeda and Phillippe Rostaing and Antoine Triller and Norman Salem and Ashe, {Karen H} and Frautschy, {Sally A.} and Cole, {Greg M.}",
year = "2004",
month = "9",
day = "2",
doi = "10.1016/j.neuron.2004.08.013",
language = "English (US)",
volume = "43",
pages = "633--645",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model

AU - Calon, Frédéric

AU - Lim, Giselle P.

AU - Yang, Fusheng

AU - Morihara, Takashi

AU - Teter, Bruce

AU - Ubeda, Oliver

AU - Rostaing, Phillippe

AU - Triller, Antoine

AU - Salem, Norman

AU - Ashe, Karen H

AU - Frautschy, Sally A.

AU - Cole, Greg M.

PY - 2004/9/2

Y1 - 2004/9/2

N2 - 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 p85α 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.

AB - 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 p85α 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.

UR - http://www.scopus.com/inward/record.url?scp=4444223956&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4444223956&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2004.08.013

DO - 10.1016/j.neuron.2004.08.013

M3 - Article

C2 - 15339646

AN - SCOPUS:4444223956

VL - 43

SP - 633

EP - 645

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 5

ER -