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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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Effects of age on cued and reference memory tasks with cued trials conducted first. A and B: Graphs showing the performance, measured as cumulative proximity in tracker system units, of 3 and 26 month old mice within cued trials in the water maze with all animals included in analysis (A) and with 4 aged mice excluded for poorer performance on cued trials than 3 standard deviations from the mean performance in the young (B). C: Graph showing the performance, measured as cumulative proximity in tracker system units, of 3 and 26 month old mice within individual place learning trials with 4 aged mice excluded. D: Graphs showing the performance, measured as cumulative proximity in tracker system units, of 3 and 26 month old mice averaged across all place learning trials. Results are for both when all mice were included (no exclusion) and when 4 old mice were excluded (4 exclusions) from analysis. * p < .05 for difference from 3 month old mice (analysis of variance and Fisher's protected least significant difference post-hoc analysis). A and D (no exclusions): n = 8 for 3 month olds and n = 10 for 26 month old mice. B, C, and D (4 exclusions): n = 8 for 3 month olds and n = 6 for 26 month old mice. Error bars represent SEM.
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Figure 3: Effects of age on cued and reference memory tasks with cued trials conducted first. A and B: Graphs showing the performance, measured as cumulative proximity in tracker system units, of 3 and 26 month old mice within cued trials in the water maze with all animals included in analysis (A) and with 4 aged mice excluded for poorer performance on cued trials than 3 standard deviations from the mean performance in the young (B). C: Graph showing the performance, measured as cumulative proximity in tracker system units, of 3 and 26 month old mice within individual place learning trials with 4 aged mice excluded. D: Graphs showing the performance, measured as cumulative proximity in tracker system units, of 3 and 26 month old mice averaged across all place learning trials. Results are for both when all mice were included (no exclusion) and when 4 old mice were excluded (4 exclusions) from analysis. * p < .05 for difference from 3 month old mice (analysis of variance and Fisher's protected least significant difference post-hoc analysis). A and D (no exclusions): n = 8 for 3 month olds and n = 10 for 26 month old mice. B, C, and D (4 exclusions): n = 8 for 3 month olds and n = 6 for 26 month old mice. Error bars represent SEM.

Mentions: There was a significant overall effect of age, F (1, 16) = 5.331, p = .0346, and there was a significant overall effect of trial, F (5, 80) = 3.714, p = .0045, on performance in cued trials when they occurred prior to the place training trials (Figure 3A). The older mice had higher cumulative proximity measurements than the young overall in the cued trials (Figure 3A). The performance averaged across cued trials 2–6 for four of the old mice was greater than 3 standard deviations from the mean of the performance of young mouse group. When these four mice were excluded from the analysis, there was no significant overall effect of age, F (1, 12) = .722, p = .41, but there was still a significant overall effect of trial, F (5, 60) = 4.437, p = .0017, on performance in cued trials that were performed prior to the place training trials (Figure 3B).


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)

Effects of age on cued and reference memory tasks with cued trials conducted first. A and B: Graphs showing the performance, measured as cumulative proximity in tracker system units, of 3 and 26 month old mice within cued trials in the water maze with all animals included in analysis (A) and with 4 aged mice excluded for poorer performance on cued trials than 3 standard deviations from the mean performance in the young (B). C: Graph showing the performance, measured as cumulative proximity in tracker system units, of 3 and 26 month old mice within individual place learning trials with 4 aged mice excluded. D: Graphs showing the performance, measured as cumulative proximity in tracker system units, of 3 and 26 month old mice averaged across all place learning trials. Results are for both when all mice were included (no exclusion) and when 4 old mice were excluded (4 exclusions) from analysis. * p < .05 for difference from 3 month old mice (analysis of variance and Fisher's protected least significant difference post-hoc analysis). A and D (no exclusions): n = 8 for 3 month olds and n = 10 for 26 month old mice. B, C, and D (4 exclusions): n = 8 for 3 month olds and n = 6 for 26 month old mice. Error bars represent SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Effects of age on cued and reference memory tasks with cued trials conducted first. A and B: Graphs showing the performance, measured as cumulative proximity in tracker system units, of 3 and 26 month old mice within cued trials in the water maze with all animals included in analysis (A) and with 4 aged mice excluded for poorer performance on cued trials than 3 standard deviations from the mean performance in the young (B). C: Graph showing the performance, measured as cumulative proximity in tracker system units, of 3 and 26 month old mice within individual place learning trials with 4 aged mice excluded. D: Graphs showing the performance, measured as cumulative proximity in tracker system units, of 3 and 26 month old mice averaged across all place learning trials. Results are for both when all mice were included (no exclusion) and when 4 old mice were excluded (4 exclusions) from analysis. * p < .05 for difference from 3 month old mice (analysis of variance and Fisher's protected least significant difference post-hoc analysis). A and D (no exclusions): n = 8 for 3 month olds and n = 10 for 26 month old mice. B, C, and D (4 exclusions): n = 8 for 3 month olds and n = 6 for 26 month old mice. Error bars represent SEM.
Mentions: There was a significant overall effect of age, F (1, 16) = 5.331, p = .0346, and there was a significant overall effect of trial, F (5, 80) = 3.714, p = .0045, on performance in cued trials when they occurred prior to the place training trials (Figure 3A). The older mice had higher cumulative proximity measurements than the young overall in the cued trials (Figure 3A). The performance averaged across cued trials 2–6 for four of the old mice was greater than 3 standard deviations from the mean of the performance of young mouse group. When these four mice were excluded from the analysis, there was no significant overall effect of age, F (1, 12) = .722, p = .41, but there was still a significant overall effect of trial, F (5, 60) = 4.437, p = .0017, on performance in cued trials that were performed prior to the place training trials (Figure 3B).

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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