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Age-related declines in a two-day reference memory task are associated with changes in NMDA receptor subunits in mice.

Magnusson KR, Scruggs B, Zhao X, Hammersmark R - BMC Neurosci (2007)

Bottom Line: NMDA receptor subunit and syntaxin proteins were analyzed with Western blotting.A significant decrease in performance was seen between 3 and 26 months of age with the two-day reference task, regardless of whether cued testing was performed before or after reference memory testing.There was a significant decline in the protein expression of the epsilon2 and zeta1 subunits of the NMDA receptor and syntaxin in prefrontal/frontal cortex.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA. Kathy.Magnusson@oregonstate.edu

ABSTRACT

Background: C57BL/6 mice show a relationship during aging between NMDA receptor expression and spatial reference memory performance in a 12-day task. The present study was designed to determine if age-related deficits could be detected with a shorter testing protocol and whether these deficits showed a relationship with NMDA receptors. Mice were trained in a reference memory task for two days in a Morris water maze. Cued testing was performed either after or prior to reference memory testing. Crude synaptosomes were prepared from prefrontal/frontal cortex and hippocampus of the mice that underwent reference memory testing first. NMDA receptor subunit and syntaxin proteins were analyzed with Western blotting.

Results: Young mice showed significant improvement in probe and place learning when reference memory testing was done prior to cued testing. A significant decrease in performance was seen between 3 and 26 months of age with the two-day reference task, regardless of whether cued testing was performed before or after reference memory testing. There was a significant decline in the protein expression of the epsilon2 and zeta1 subunits of the NMDA receptor and syntaxin in prefrontal/frontal cortex. The subunit changes showed a significant correlation with both place and probe trial performance.

Conclusion: The presence of an age-related decline in performance of the reference memory task regardless of when the cued trials were performed suggests that the deficits were due to factors that were unique to the spatial reference memory task. These results also suggest that declines in specific NMDA receptor subunits in the synaptic pool of prefrontal/frontal brain regions contributed to these age-related problems with performing a spatial reference memory task.

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Relationships between reference memory performance and protein expression of NMDA receptor subunits. A, B: Correlation graphs of ζ1 (A) and ε2 (B) expression in the prefrontal/frontal cortex versus averaged place (A) or learning index score (B) derived from probe trial performance in a two-day reference memory task. Correlation coefficients are presented in Table 1. Proximity measurements are given in tracker system units.
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Figure 5: Relationships between reference memory performance and protein expression of NMDA receptor subunits. A, B: Correlation graphs of ζ1 (A) and ε2 (B) expression in the prefrontal/frontal cortex versus averaged place (A) or learning index score (B) derived from probe trial performance in a two-day reference memory task. Correlation coefficients are presented in Table 1. Proximity measurements are given in tracker system units.

Mentions: There were significant negative correlations for both the overall cumulative proximity measurements in the place trials and the learning index scores derived from the probe trials and subunit equivalents/μg protein for the ζ1 and ε2 subunits in crude synaptosomes from the prefrontal/frontal cortex when all animals were considered (Table 1 and Figure 5). The negative correlation coefficient indicated that high levels of protein expression were associated with low proximity measurements or learning index scores (i.e., good performance in the water maze). There were no significant correlations found for protein expression of the ε1 subunit or syntaxin in the prefrontal/frontal cortex and performance in either the place or probe trials across the ages (Table 1). None of the subunits nor syntaxin expression levels in the hippocampus showed a significant correlation with place or probe trial performance across the ages (Table 1). There was a near significant correlation between the protein expression of the ε2 subunit in the hippocampus of young alone (R = -757, p = .086) and old alone (R = -77, p = .077) and the learning index score. There was a significant correlation between syntaxin expression in the hippocampus of the old group alone and the learning index score (R = -.832, p = .038).


Age-related declines in a two-day reference memory task are associated with changes in NMDA receptor subunits in mice.

Magnusson KR, Scruggs B, Zhao X, Hammersmark R - BMC Neurosci (2007)

Relationships between reference memory performance and protein expression of NMDA receptor subunits. A, B: Correlation graphs of ζ1 (A) and ε2 (B) expression in the prefrontal/frontal cortex versus averaged place (A) or learning index score (B) derived from probe trial performance in a two-day reference memory task. Correlation coefficients are presented in Table 1. Proximity measurements are given in tracker system units.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1919384&req=5

Figure 5: Relationships between reference memory performance and protein expression of NMDA receptor subunits. A, B: Correlation graphs of ζ1 (A) and ε2 (B) expression in the prefrontal/frontal cortex versus averaged place (A) or learning index score (B) derived from probe trial performance in a two-day reference memory task. Correlation coefficients are presented in Table 1. Proximity measurements are given in tracker system units.
Mentions: There were significant negative correlations for both the overall cumulative proximity measurements in the place trials and the learning index scores derived from the probe trials and subunit equivalents/μg protein for the ζ1 and ε2 subunits in crude synaptosomes from the prefrontal/frontal cortex when all animals were considered (Table 1 and Figure 5). The negative correlation coefficient indicated that high levels of protein expression were associated with low proximity measurements or learning index scores (i.e., good performance in the water maze). There were no significant correlations found for protein expression of the ε1 subunit or syntaxin in the prefrontal/frontal cortex and performance in either the place or probe trials across the ages (Table 1). None of the subunits nor syntaxin expression levels in the hippocampus showed a significant correlation with place or probe trial performance across the ages (Table 1). There was a near significant correlation between the protein expression of the ε2 subunit in the hippocampus of young alone (R = -757, p = .086) and old alone (R = -77, p = .077) and the learning index score. There was a significant correlation between syntaxin expression in the hippocampus of the old group alone and the learning index score (R = -.832, p = .038).

Bottom Line: NMDA receptor subunit and syntaxin proteins were analyzed with Western blotting.A significant decrease in performance was seen between 3 and 26 months of age with the two-day reference task, regardless of whether cued testing was performed before or after reference memory testing.There was a significant decline in the protein expression of the epsilon2 and zeta1 subunits of the NMDA receptor and syntaxin in prefrontal/frontal cortex.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA. Kathy.Magnusson@oregonstate.edu

ABSTRACT

Background: C57BL/6 mice show a relationship during aging between NMDA receptor expression and spatial reference memory performance in a 12-day task. The present study was designed to determine if age-related deficits could be detected with a shorter testing protocol and whether these deficits showed a relationship with NMDA receptors. Mice were trained in a reference memory task for two days in a Morris water maze. Cued testing was performed either after or prior to reference memory testing. Crude synaptosomes were prepared from prefrontal/frontal cortex and hippocampus of the mice that underwent reference memory testing first. NMDA receptor subunit and syntaxin proteins were analyzed with Western blotting.

Results: Young mice showed significant improvement in probe and place learning when reference memory testing was done prior to cued testing. A significant decrease in performance was seen between 3 and 26 months of age with the two-day reference task, regardless of whether cued testing was performed before or after reference memory testing. There was a significant decline in the protein expression of the epsilon2 and zeta1 subunits of the NMDA receptor and syntaxin in prefrontal/frontal cortex. The subunit changes showed a significant correlation with both place and probe trial performance.

Conclusion: The presence of an age-related decline in performance of the reference memory task regardless of when the cued trials were performed suggests that the deficits were due to factors that were unique to the spatial reference memory task. These results also suggest that declines in specific NMDA receptor subunits in the synaptic pool of prefrontal/frontal brain regions contributed to these age-related problems with performing a spatial reference memory task.

Show MeSH