Behavioural NeuroscienceResearch PaperThe effects of aging on N-methyl-d-aspartate receptor subunits in the synaptic membrane and relationships to long-term spatial memory
Section snippets
Animals
Thirty-four, male C57BL/6JNIAHSD mice (National Institute on Aging, Bethesda, MD, USA) from three different age groups (4, 11, and 26 months of age at time of behavioral testing and euthanasia) were used. Mice were ad libitum–fed and housed under 12-h light/dark conditions for 1.5 months prior to and during behavioral testing at University of Idaho. All animal procedures were approved by the Institutional Animal Care and Use Committee at University of Idaho and conformed to NIH guidelines.
Behavioral testing results
There was a significant main effect of age (F(2,31)=7.5, P=0.002) and trial block (F(7,217)=11.6; P<0.0001) on corrected cumulative proximity in the place training trials (Fig. 2A, B). The 26-month-old mice had significantly higher corrected cumulative proximity than both the 4- (P=0.002) and 11- (P=0.017) month-old mice when data were averaged across all blocks of place trials (Fig. 2B). The 4- (P=0.0003) and 11- (P=0.0002) month-old mice had significantly lower corrected cumulative
Discussion
There were four major findings in this study. (1) The results of this study support the hypothesis that there was a greater decline during aging in the protein expression of the NR2B subunit within the synaptic membrane of the frontal cortex than in the tissue as a whole. (2) In the hippocampus, the expression of the NR2B subunit showed similar declines between whole homogenate and synaptic membranes. (3) Both the NR2B and NR1 subunits of the NMDA receptor within the synaptic membranes of the
Conclusion
In conclusion, there were differences in the effects of aging on expression of the NR2B subunit within frontal cortex versus the hippocampus. In the frontal cortex there appeared to be an effect of aging on the localization of the NR2B subunit of the NMDA receptor to the synaptic membrane that was greater than changes in whole cell expression. The changes in synaptic expression of the NR2B subunit in the hippocampus appeared to be more related to declines throughout the cell, suggesting a
Acknowledgments
This work was supported by NIH grant AG16322 to K.R.M. We would also like to thank David G. Standaert for his advice on the subfractionation protocol.
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