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Hippocampal Cortactin Levels are Reduced Following Spatial Working Memory Formation, an Effect Blocked by Chronic Calpain Inhibition.

Olson ML, Ingebretson AE, Harmelink KM - Brain Sci (2015)

Bottom Line: Because cortactin is a substrate of the cysteine protease calpain, we also assessed the effect of chronic calpain inhibition on RAM performance and cortactin expression.Calpain inhibition impaired spatial working memory and blocked the reduction in hippocampal cortactin levels following RAM training.These findings add to a growing body of research implicating cortactin and calpain in hippocampus-dependent memory formation.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology and Program in Neuroscience, Concordia College, Moorhead, MN 56562, USA. molson@cord.edu.

ABSTRACT
The mechanism by which the hippocampus facilitates declarative memory formation appears to involve, among other things, restructuring of the actin cytoskeleton within neuronal dendrites. One protein involved in this process is cortactin, which is an important link between extracellular signaling and cytoskeletal reorganization. In this paper, we demonstrate that total hippocampal cortactin, as well as Y421-phosphorylated cortactin are transiently reduced following spatial working memory formation in the radial arm maze (RAM). Because cortactin is a substrate of the cysteine protease calpain, we also assessed the effect of chronic calpain inhibition on RAM performance and cortactin expression. Calpain inhibition impaired spatial working memory and blocked the reduction in hippocampal cortactin levels following RAM training. These findings add to a growing body of research implicating cortactin and calpain in hippocampus-dependent memory formation.

No MeSH data available.


Related in: MedlinePlus

Chronic calpain inhibition blocks the reduction in total, but not Y421-phosphorylated cortactin following spatial working memory formation in the RAM. Representative samples and graphical depictions of group means for hippocampal total, and Y421-phosphorylated, cortactin (±SEM; expressed as percent of untrained controls) at 30 min following RAM training for Veh and Cal-I groups. * p < 0.05 compared to untrained controls, ** p < 0.05 compared to both untrained control and Cal-I groups.
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brainsci-05-00241-f005: Chronic calpain inhibition blocks the reduction in total, but not Y421-phosphorylated cortactin following spatial working memory formation in the RAM. Representative samples and graphical depictions of group means for hippocampal total, and Y421-phosphorylated, cortactin (±SEM; expressed as percent of untrained controls) at 30 min following RAM training for Veh and Cal-I groups. * p < 0.05 compared to untrained controls, ** p < 0.05 compared to both untrained control and Cal-I groups.

Mentions: Figure 5 shows a representative immunoblot and graphical representations of hippocampal cortactin and Y421-phosphorylated cortactin expression in untrained, Veh, and Cal- I rats. Due to limitations in the number of wells on a single electrophoresis gel (10 wells per gel), only two groups (N = 4/group) could be analyzed on a gel at a time. Because of this, protein levels from each of the groups were compared to each other using a series of T-tests. For illustrative purposes, Figure 5 includes images of gels that were run N = 2 per group to depict group differences visually on a single electrophoresis gel. Furthermore, the graphical representation in Figure 5 consists of data that was collapsed across gels (N = 4/group) by normalizing total protein stain values from the untrained group. This was done to simplify visual depiction of our results; however, because normalization can introduce error, statistical comparisons were made only within each individual gel, thus comparing only two groups at a time. Results for total cortactin levels revealed a significant reduction in the Veh group compared to untrained controls T(6) = 2.832, p = 0.03; thus replicating our results from experiment 1. Further, our data demonstrate significantly higher cortactin expression in Cal-I rats compared to the Veh group T(6) = 4.498, p = 0.004. Taken together, these findings indicate that chronic calpain inhibition blocks the training-induced reduction in cortactin following spatial learning in the RAM. Results for Y421-phosphorylated cortactin showed a significant difference between untrained and Veh groups with the Veh group showing a reduction T(6) = 6.324, p = 0.001, again replicating our results from experiment 1. However, we also observed significant differences between untrained and Cal-I groups T(6) = 3.245, p = 0.018 and between the Veh and Cal-I groups T(6) = −2.641, p = 0.038. This indicates that calpain inhibition significantly attenuates the reduction in Y421-phosphorylated cortactin following RAM training, but Y421-phosphorylated cortactin is still significantly reduced in the presence of calpain inhibitors.


Hippocampal Cortactin Levels are Reduced Following Spatial Working Memory Formation, an Effect Blocked by Chronic Calpain Inhibition.

Olson ML, Ingebretson AE, Harmelink KM - Brain Sci (2015)

Chronic calpain inhibition blocks the reduction in total, but not Y421-phosphorylated cortactin following spatial working memory formation in the RAM. Representative samples and graphical depictions of group means for hippocampal total, and Y421-phosphorylated, cortactin (±SEM; expressed as percent of untrained controls) at 30 min following RAM training for Veh and Cal-I groups. * p < 0.05 compared to untrained controls, ** p < 0.05 compared to both untrained control and Cal-I groups.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493467&req=5

brainsci-05-00241-f005: Chronic calpain inhibition blocks the reduction in total, but not Y421-phosphorylated cortactin following spatial working memory formation in the RAM. Representative samples and graphical depictions of group means for hippocampal total, and Y421-phosphorylated, cortactin (±SEM; expressed as percent of untrained controls) at 30 min following RAM training for Veh and Cal-I groups. * p < 0.05 compared to untrained controls, ** p < 0.05 compared to both untrained control and Cal-I groups.
Mentions: Figure 5 shows a representative immunoblot and graphical representations of hippocampal cortactin and Y421-phosphorylated cortactin expression in untrained, Veh, and Cal- I rats. Due to limitations in the number of wells on a single electrophoresis gel (10 wells per gel), only two groups (N = 4/group) could be analyzed on a gel at a time. Because of this, protein levels from each of the groups were compared to each other using a series of T-tests. For illustrative purposes, Figure 5 includes images of gels that were run N = 2 per group to depict group differences visually on a single electrophoresis gel. Furthermore, the graphical representation in Figure 5 consists of data that was collapsed across gels (N = 4/group) by normalizing total protein stain values from the untrained group. This was done to simplify visual depiction of our results; however, because normalization can introduce error, statistical comparisons were made only within each individual gel, thus comparing only two groups at a time. Results for total cortactin levels revealed a significant reduction in the Veh group compared to untrained controls T(6) = 2.832, p = 0.03; thus replicating our results from experiment 1. Further, our data demonstrate significantly higher cortactin expression in Cal-I rats compared to the Veh group T(6) = 4.498, p = 0.004. Taken together, these findings indicate that chronic calpain inhibition blocks the training-induced reduction in cortactin following spatial learning in the RAM. Results for Y421-phosphorylated cortactin showed a significant difference between untrained and Veh groups with the Veh group showing a reduction T(6) = 6.324, p = 0.001, again replicating our results from experiment 1. However, we also observed significant differences between untrained and Cal-I groups T(6) = 3.245, p = 0.018 and between the Veh and Cal-I groups T(6) = −2.641, p = 0.038. This indicates that calpain inhibition significantly attenuates the reduction in Y421-phosphorylated cortactin following RAM training, but Y421-phosphorylated cortactin is still significantly reduced in the presence of calpain inhibitors.

Bottom Line: Because cortactin is a substrate of the cysteine protease calpain, we also assessed the effect of chronic calpain inhibition on RAM performance and cortactin expression.Calpain inhibition impaired spatial working memory and blocked the reduction in hippocampal cortactin levels following RAM training.These findings add to a growing body of research implicating cortactin and calpain in hippocampus-dependent memory formation.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology and Program in Neuroscience, Concordia College, Moorhead, MN 56562, USA. molson@cord.edu.

ABSTRACT
The mechanism by which the hippocampus facilitates declarative memory formation appears to involve, among other things, restructuring of the actin cytoskeleton within neuronal dendrites. One protein involved in this process is cortactin, which is an important link between extracellular signaling and cytoskeletal reorganization. In this paper, we demonstrate that total hippocampal cortactin, as well as Y421-phosphorylated cortactin are transiently reduced following spatial working memory formation in the radial arm maze (RAM). Because cortactin is a substrate of the cysteine protease calpain, we also assessed the effect of chronic calpain inhibition on RAM performance and cortactin expression. Calpain inhibition impaired spatial working memory and blocked the reduction in hippocampal cortactin levels following RAM training. These findings add to a growing body of research implicating cortactin and calpain in hippocampus-dependent memory formation.

No MeSH data available.


Related in: MedlinePlus