Higher levels of phosphorylated Y1472 on GluN2B subunits in the frontal cortex of aged mice are associated with good spatial reference memory, but not cognitive flexibility
| العنوان: | Higher levels of phosphorylated Y1472 on GluN2B subunits in the frontal cortex of aged mice are associated with good spatial reference memory, but not cognitive flexibility |
|---|---|
| المؤلفون: | Val Elias, Kathy R. Magnusson, Varinia A. Acosta, Daniel R. Zamzow, Emily Escobedo |
| المصدر: | AGE. 38 |
| بيانات النشر: | Springer Science and Business Media LLC, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Aging, medicine.medical_specialty, Protein subunit, Morris water navigation task, Hippocampus, Receptors, N-Methyl-D-Aspartate, Article, Mice, 03 medical and health sciences, Cognition, 0302 clinical medicine, Internal medicine, medicine, Animals, Aging brain, Phosphorylation, Maze Learning, Receptor, biology, Cognitive flexibility, Calpain, General Medicine, Frontal Lobe, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Frontal lobe, biology.protein, NMDA receptor, Geriatrics and Gerontology, Neuroscience, 030217 neurology & neurosurgery |
| الوصف: | The N-methyl-d-aspartate receptor (NMDAr) is particularly vulnerable to aging. The GluN2B subunit of the NMDAr, compared to other NMDAr subunits, suffers the greatest losses of expression in the aging brain, especially in the frontal cortex. While expression levels of GluN2B mRNA and protein in the aged brain are well documented, there has been little investigation into age-related posttranslational modifications of the subunit. In this study, we explored some of the mechanisms that may promote differences in the NMDAr complex in the frontal cortex of aged animals. Two ages of mice, 3 and 24 months, were behaviorally tested in the Morris water maze. The frontal cortex and hippocampus from each mouse were subjected to differential centrifugation followed by solubilization in Triton X-100. Proteins from Triton-insoluble membranes, Triton-soluble membranes, and intracellular membranes/cytosol were examined by Western blot. Higher levels of GluN2B tyrosine 1472 phosphorylation in frontal cortex synaptic fractions of old mice were associated with better reference learning but poorer cognitive flexibility. Levels of GluN2B phosphotyrosine 1336 remained steady, but there were greater levels of the calpain-induced 115 kDa GluN2B cleavage product on extrasynaptic membranes in these old good learners. There was an age-related increase in calpain activity, but it was not associated with better learning. These data highlight a unique aging change for aged mice with good spatial learning that might be detrimental to cognitive flexibility. This study also suggests that higher levels of truncated GluN2B on extrasynaptic membranes are not deleterious to spatial memory in aged mice. |
| تدمد: | 1574-4647 0161-9152 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5f19d980163bdbc9268e01ce144e7b84 https://doi.org/10.1007/s11357-016-9913-2 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....5f19d980163bdbc9268e01ce144e7b84 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15744647 01619152 |
|---|