Abstract
Aging is known to alter many physiological processes within the brain including synaptic responses, long-term potentiation, 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 that might underlie age-related deficits in neuronal physiology.
Highlights
From the ‡Medical Scientist Training Program, the §Neuroscience Program, and the ¶Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262
In this report we extend those findings by examining the surface expression of the NMDA receptor subunits in the CA1 region of the hippocampus in 6, 16, and 24-month-old Fischer 344 rats
We have found that aging does not affect the basal surface expression of NMDA receptors
Summary
From the ‡Medical Scientist Training Program, the §Neuroscience Program, and the ¶Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80262. 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 activitydependent changes in the surface distribution of NMDA receptors. In conjunction with this observation we have noted that aged rats show an expression deficit in the C2 splice variant of the NR1 subunit. The N-methyl-D-aspartate (NMDA) receptor is thought to play an important role in neuronal signaling because of its ability to flux calcium This occurs in response to glutamate and concomitant depolarization, allowing the NMDA receptor to function as a “coincidence detector.”. We examined the expression of NR1 splice variants in aged animals
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