Studies of electrophysiological activity in the brains of the mice showed that the two-week p25 animals showed enhancement in the mechanism called "long-term potentiation" (LTP), which is central to learning and memory processes. In contrast, the six-week p25 animals showed a decrease in LTP.
Also, microscopy studies revealed that the two-week p25 animals showed higher connectivity among their neurons than did the six-week p25 animals.
The researchers concluded that their findings "indicate that transient p25 production facilitated learning, whereas the ability to form new memories was impaired by prolonged p25 expression." Also, they wrote that their data suggest that Cdk5 activity plays a role in the adult brain in forming new connections among neurons.
"It is possible that p25 is produced to compensate for the loss of Cdk5 activity during aging," they wrote. "In this scenario, chronic exposure to AD risk factors would further increase p25 levels to a critical concentration that ultimately contributes to neuronal loss.
"Taken together these data suggest that p25 production in vivo is not detrimental per se but can lead to neuronal cell death when p25 levels are chronically high," concluded Tsai and colleagues.
"In summary, it is intriguing that several studies suggest that during the pathogenesis of AD, which manifests over several years, compensatory mechanisms that initially enhance neuroplasticity eventually become maladaptive when chronically activated," they wrote. "A similar scenario can be envisioned for p25. Thus, the present study provides evidence that p25 generation might be a compensatory phenomenon to enhance neuroplasticity. These mice may also serve as a model whereby a factor that promotes plasticity can eventually contribute to neurodegeneration," they wrote.
'"/>
Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
7-Dec-2005