Exploring the Interaction between TSC2, PTEN, and the NMDA Receptor in Animal Models of Tuberous Sclerosis
Final rept. 1 Jul 2012-30 Jun 2014
RUTGERS - THE STATE UNIV NEW BRUNSWICK NJ
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In this study we investigated the relationship between Pten, Tsc2 and the NMDA receptor using conditional knock out mice. We originally hypothesized that loss of Tsc2 could alter NMDA receptor expression through a mechanism that may involve Pten downregulation, rather than changes in mTOR signaling. The data generated during the course of this study conclusively demonstrate that Pten loss in the forebrain leads to alterations in the expression of all major NMDA receptor subunits. However, Tsc2 loss in the same brain cells does not affect the NMDA receptor. Also, we found that Tsc2 loss does not affect Pten levels. Taken together, our findings suggest that Pten controls NMDA receptor expression through a mechanism that is independent of mTOR signaling and is not affected by Tsc2 activity. Further studies will be required to determine whether Pten affects NMDA receptor expression through direct protein-protein interaction, or through Akt-dependent signaling. Overall, our results suggest that NMDA receptor abnormalities do not play a central role in cognitive defects in TSC patients.
- Medicine and Medical Research