期刊
NEURON
卷 43, 期 5, 页码 633-645出版社
CELL PRESS
DOI: 10.1016/j.neuron.2004.08.013
关键词
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资金
- NIA NIH HHS [P50 AG05142, AG16793, R01 AG010685, R01 AG13741, P50 AG016570, AG10685, P01 AG16570, P50 AG 16570, R01 AG013741, P50 AG005142, R01 AG016793] Funding Source: Medline
- NINDS NIH HHS [R01 NS043946, NS43946] Funding Source: Medline
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.
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