• 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, and Greg M Cole.
• Department of Medicine, University of California, Los Angeles, 90095, USA.
• Neuron. 2004 Sep 2; 43 (5): 633-45.

AbstractLearning 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.

60 keywords...

hide…