Faculty Opinions recommendation of Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model.

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 Funding information This work was supported by: NIA NIH HHS, United States Grant ID: R01 AG010685 NINDS NIH HHS, United States Grant ID: NS43946 NIA NIH HHS, United States Grant ID: P50 AG016570 NIA NIH HHS, United States Grant ID: R01 AG013741 NIA NIH HHS, United States Grant ID: R01 AG016793 NIA NIH HHS, United States Grant ID: P50 AG 16570 NIA NIH HHS, United States Grant ID: AG16793 NIA NIH HHS, United States Grant ID: P50 AG05142 NIA NIH HHS, United States Grant ID: P01 AG16570 NIA NIH HHS, United States Grant ID: R01 AG13741 NINDS NIH HHS, United States Grant ID: R01 NS043946 NIA NIH HHS, United States Grant ID: P50 AG005142 NIA NIH HHS, United States Grant ID: AG10685 More Less keyboard_arrow_down