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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

Cortactin is transiently reduced 30 min after RAM training. Representative immunoblots and group means for hippocampal cortactin (±SEM; expressed as percent of untrained controls) at 5 min, 30 min, and 4 h following RAM training. * p < 0.05 compared to untrained controls.
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brainsci-05-00241-f002: Cortactin is transiently reduced 30 min after RAM training. Representative immunoblots and group means for hippocampal cortactin (±SEM; expressed as percent of untrained controls) at 5 min, 30 min, and 4 h following RAM training. * p < 0.05 compared to untrained controls.

Mentions: Figure 2 shows representative immunoblots and graphical representations, expressed as percent of untrained controls, of hippocampal cortactin expression in untrained animals and animals in the 5 min, 30 min, and 4 h experimental groups. While there were no significant differences between the groups at 5 min T(6) = −1.636, p = 0.15 and only a marginal difference at 4 h T(6) = 2.276, p = 0.07, there was a significant reduction in total cortactin observed at 30 min T(6) = 2.751, p = 0.033. Figure 3 presents corresponding data for Y421-phoshphorylated cortactin. Similarly, no significant differences were observed between the untrained group and either the 5 min T(6) = 1.417, p = 0.20 or 4 h T(6) = −0.016, p = 0.99 time points. However, as with the total cortactin data, there was a significant reduction in Y421-phosphorylated cortactin in the hippocampus of the 30 min group T(6) = 3.678, p = 0.01.


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)

Cortactin is transiently reduced 30 min after RAM training. Representative immunoblots and group means for hippocampal cortactin (±SEM; expressed as percent of untrained controls) at 5 min, 30 min, and 4 h following RAM training. * p < 0.05 compared to untrained controls.
© Copyright Policy
Related In: Results  -  Collection

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

brainsci-05-00241-f002: Cortactin is transiently reduced 30 min after RAM training. Representative immunoblots and group means for hippocampal cortactin (±SEM; expressed as percent of untrained controls) at 5 min, 30 min, and 4 h following RAM training. * p < 0.05 compared to untrained controls.
Mentions: Figure 2 shows representative immunoblots and graphical representations, expressed as percent of untrained controls, of hippocampal cortactin expression in untrained animals and animals in the 5 min, 30 min, and 4 h experimental groups. While there were no significant differences between the groups at 5 min T(6) = −1.636, p = 0.15 and only a marginal difference at 4 h T(6) = 2.276, p = 0.07, there was a significant reduction in total cortactin observed at 30 min T(6) = 2.751, p = 0.033. Figure 3 presents corresponding data for Y421-phoshphorylated cortactin. Similarly, no significant differences were observed between the untrained group and either the 5 min T(6) = 1.417, p = 0.20 or 4 h T(6) = −0.016, p = 0.99 time points. However, as with the total cortactin data, there was a significant reduction in Y421-phosphorylated cortactin in the hippocampus of the 30 min group T(6) = 3.678, p = 0.01.

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