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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 reference memory and cued tasks with cued trials conducted last. A and C: Graphs showing the performance, measured as cumulative proximity in tracker system units, of 3 and 26 month old mice within individual place learning trials (A) and averaged across all place learning trials (C). B: Graph showing the performance, measured as average proximity in tracker system units, of 3 and 26 month old mice within individual probe trials. D: Individual learning index scores with the horizontal bar indicating the mean for each age group. E: Graph 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. * p < .05 for difference from 3 month old mice (analysis of variance and Fisher's protected least significant difference post-hoc analysis). n = 8 for 3 month olds and n = 6 for 26 month old mice. Error bars represent SEM.
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Figure 2: Effects of age on reference memory and cued tasks with cued trials conducted last. A and C: Graphs showing the performance, measured as cumulative proximity in tracker system units, of 3 and 26 month old mice within individual place learning trials (A) and averaged across all place learning trials (C). B: Graph showing the performance, measured as average proximity in tracker system units, of 3 and 26 month old mice within individual probe trials. D: Individual learning index scores with the horizontal bar indicating the mean for each age group. E: Graph 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. * p < .05 for difference from 3 month old mice (analysis of variance and Fisher's protected least significant difference post-hoc analysis). 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, 12) = 22.785, p = .0005, and trial, F (15, 180) = 3.135, p = .0001, on performance in place learning trials (Figure 2A, C). There was also a significant interaction between age and trial, F (15, 180) = 2.408, p = .0033, on place learning performance. The 26 months olds had significantly greater cumulative proximity measurements than 3-month-old mice when performance was averaged across all place trials (Figure 2C). The 3 month olds showed a significant reduction in cumulative proximity between the first place trial of Day 1 and last trial of Day 2 (trial 16; p = .0041), but not between the first and eighth (last trial of Day 1) place trials (p = .2225; Figure 2A). The 26-month-old mice showed only a near significant decrease (p = .0641) in cumulative proximity from the first to the last place trial and no significant change between place trials 1 and 8 (Day 1; p = .2313; Figure 2A). There was no significant main effect of age, F (1, 12) = 3.396, p = .0902, on cumulative proximity measurements across place learning trials 1 through 8 (Day 1; Figure 2A).


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 reference memory and cued tasks with cued trials conducted last. A and C: Graphs showing the performance, measured as cumulative proximity in tracker system units, of 3 and 26 month old mice within individual place learning trials (A) and averaged across all place learning trials (C). B: Graph showing the performance, measured as average proximity in tracker system units, of 3 and 26 month old mice within individual probe trials. D: Individual learning index scores with the horizontal bar indicating the mean for each age group. E: Graph 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. * p < .05 for difference from 3 month old mice (analysis of variance and Fisher's protected least significant difference post-hoc analysis). 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 2: Effects of age on reference memory and cued tasks with cued trials conducted last. A and C: Graphs showing the performance, measured as cumulative proximity in tracker system units, of 3 and 26 month old mice within individual place learning trials (A) and averaged across all place learning trials (C). B: Graph showing the performance, measured as average proximity in tracker system units, of 3 and 26 month old mice within individual probe trials. D: Individual learning index scores with the horizontal bar indicating the mean for each age group. E: Graph 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. * p < .05 for difference from 3 month old mice (analysis of variance and Fisher's protected least significant difference post-hoc analysis). 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, 12) = 22.785, p = .0005, and trial, F (15, 180) = 3.135, p = .0001, on performance in place learning trials (Figure 2A, C). There was also a significant interaction between age and trial, F (15, 180) = 2.408, p = .0033, on place learning performance. The 26 months olds had significantly greater cumulative proximity measurements than 3-month-old mice when performance was averaged across all place trials (Figure 2C). The 3 month olds showed a significant reduction in cumulative proximity between the first place trial of Day 1 and last trial of Day 2 (trial 16; p = .0041), but not between the first and eighth (last trial of Day 1) place trials (p = .2225; Figure 2A). The 26-month-old mice showed only a near significant decrease (p = .0641) in cumulative proximity from the first to the last place trial and no significant change between place trials 1 and 8 (Day 1; p = .2313; Figure 2A). There was no significant main effect of age, F (1, 12) = 3.396, p = .0902, on cumulative proximity measurements across place learning trials 1 through 8 (Day 1; Figure 2A).

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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