By Erene Mina. As evidence mounts against oligomers as culprits of Aβ neurotoxicity (see ARF related New Orleans story), their only defense hinges on the possibility that they may have some normal physiological function—even a slightly neurotrophic effect—on cognition which has yet to be characterized. Sally Frautschy’s group at the VA Medical Center in Sepulveda, California, presented data at the 33rd Annual Meeting of the Society for Neuroscience suggesting that Aβ oligomers can be acutely beneficial for spatial memory performance in rats, but that chronic exposure eventually leads to cognitive decline that parallels Alzheimer’s pathogenesis (SfN abstract 240.11).
Presenting author Marni Harris-White and colleagues infused rats with synthetic, SDS-stable low-molecular weight Aβ oligomers (monomers, dimers, trimers) using a mini osmotic pump that continually delivered the Aβ into a cerebral ventricle. Throughout the 3-month infusion, the researchers tested spatial memory at 6, 9, and 12 weeks in the Morris water maze. The rats spent 3 days training to swim to a visible platform, and then the researchers tested acquisition using a hidden platform. To test for memory retention, the rats attempted the maze again following a 24-hour delay. The researchers reported a steady improvement in memory acquisition and retention starting at 6 weeks and carrying through until 9 weeks post-infusion. However, by 12 weeks post-infusion, the animals began to show a mild decline in acquisition coupled with more pronounced deficits in spatial memory retention, characterized by the rats spending less time in the target quadrant. This apparent worsening of memory retention was correlated with a reduction in crucial post-synaptic proteins, such as PSD-95, in the cortex and hippocampus.
In summary, soluble, low-molecular-weight β-amyloid oligomers seem to support memory acquisition and retention early on. However, their contribution to excitatory neurotransmission is short-lived, as this initially beneficial synaptic stimulation eventually sentences the brain to cognitive deterioration. What remains to be elucidated is how an arguably toxic species of Aβ can be even remotely beneficial or have trophic activity in neurons, proving that this is no open-and-shut case. You can view abstracts mentioned in this story at the SfN/ScholarOne website.—Erene Mina is a graduate student at the University of California, Irvine.
No Available Further Reading