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Papers In Press, published online ahead of print March 12, 2002
J. Biol. Chem, 10.1074/jbc.C200074200
Submitted on February 6, 2002
Revised on March 11, 2002
Accepted on March 12, 2002

Aging and surface expression of hippocampal NMDA receptors

Daniel A. Clayton, David R. Grosshans, and Michael D. Browning

Pharmacology, UCHSC, Denver, CO 80262

Corresponding Author: michael.browning{at}uchsc.edu

Aging is known to alter many physiological processes within the brain including synaptic responses, long-term potentiation (LTP) and learning and memory. Aging has also been shown to alter the expression and distribution of N-methyl-D-aspartate (NMDA) receptors in many different brain regions, including the hippocampus. Additionally, we have recently reported that young adult rats show an activity-dependent increase in the surface expression of NMDA receptors. We have extended these observations in the present study in aged animals and have found that aged Fischer 344 rats fail to show activity dependent changes in the surface distribution of NMDA receptors. In conjunction with this observation we have also noted that aged rats show an expression deficit in the C2 splice variant of the NR1 subunit. This subunit is preferentially shifted to the surface following stimulation in young adult animals. As the NMDA receptor is thought to play an important role in neuronal signaling, these observations suggest possible new areas of dysfunction in this receptor which might underlie age-related deficits in neuronal physiology.


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