Age-related changes in the protein expression of subunits of the NMDA receptor.
C57Bl/6 mice show decreased expression of the mRNA for the epsilon2 and zeta1 subunits of the N-methyl-D-aspartate (NMDA) receptor in subregions of the cerebral cortex and hippocampus with increased age. The purpose of this study was to determine the effects of aging on the protein expression of the three major subunits of the NMDA receptor. Semi-quantitative Western blot techniques were applied with the use of antibodies that recognize either the epsilon1 (NR2A), epsilon2 (NR2B) or zeta1 (NR1) subunits of the NMDA receptor or a synaptic terminal protein, synaptophysin. In the cerebral cortex of 30-month-old mice, the level of protein expression of both the epsilon2 and zeta1 subunits were decreased significantly from levels found in the 3- and 10-month-old mice and the protein expression of the epsilon1 subunit showed a significant decline between 10 and 30 months of age. In the hippocampus, the epsilon2 subunit exhibited a higher protein expression level in the 10-month-old mice as compared to both the young and old mice and the zeta1 subunit showed a significant drop in expression in the old mice from both 3- and 10-month-olds. Synaptophysin showed significant declines in protein expression with increasing age. These results demonstrated that changes in the protein expression of the major subunits of the NMDA receptor occur during the aging process and, in some cases, were greater than changes seen previously in mRNA expression. These subunit alterations may explain some of the changes that are seen in NMDA receptor functions during aging.
Magnusson
Kathy Ruth
KR
Department of Anatomy and Neurobiology, Program in Cellular, Molecular, and Integrative Neurosciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA. kathy.magnusson@colostate.edu
Nelson
Scott Edward
SE
Young
Anne B
AB
D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D016708:Synaptophysin / Q000378:metabolism
D018685:Anesthetics, Inhalation; C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D016708:Synaptophysin