Omega-3 Fatty Acid Protects Against Neurodegeneration
September 2, 2004
NEW YORK (Reuters Health) Sept 01 - In a transgenic mouse model of Alzheimer's disease (AD), dietary supplementation with the omega-3 fatty acid docosahexaenoic acid (DHA) prevents the synaptic damage and memory loss associated with the disease, according to a paper in the September 2nd issue of Neuron.
However, when these transgenic mice consume a diet depleted of DHA, oxidative stress resulting in synaptic damage is much greater than occurs in control mice on the same diet.
Dr. Greg M. Cole, at University of California, Los Angeles, and his team found that transgenic mice expressing the human mutant amyloid precursor protein (Tg+ animals), in which brain amyloid deposition is abundant, experienced very little synaptic marker loss. Further investigation revealed that the high DHA content in their food was neuroprotective.
When 17-month-old mice were fed a diet depleted in DHA, the investigators observed decreased levels of DHA in the frontal cortex of TG+ mice, but not in Tg- mice.
The increased oxidative stress from depleted DHA in the Tg+ mice "is accompanied by postsynaptic caspase-mediated actin cleavage and the loss of the actin-regulating dendritic spine protein drebin" and postsynaptic density protein-95 (PSD-95), the authors report. When they examined brain tissue from patients with AD and control subjects, there were similar losses of drebrin and PSD-95 in the AD brains only.
Testing with the Morris water maze showed profound performance deficits when Tg+ mice were placed on a low DHA diet. These performance deficits were prevented by dietary DHA supplementation. Tg+ mice fed DHA were able to learn how to find hidden platforms in water maze, as were control mice on either a DHA-depleted or DHA-repleted diet.
Their findings are evidence that the combination of genetic and environmental risk factors -- such as DHA deficiency -- for AD can act synergistically to reduce synaptic proteins required for cognition, Dr. Cole's group maintains.
They speculate that patients with a genetic risk of AD may be more vulnerable than others to a lack of essential fatty acids. Their data thus "support the idea that increased DHA intake should be considered as a potential neuroprotective strategy for AD," they write.