Glycogen synthase kinase-3 inhibition prevents learning deficits in diabetic mice
Autor: | Lucie S. Guernsey, Matthew R. King, Corinne G. Jolivalt, Nicholas J. Anderson |
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Rok vydání: | 2012 |
Předmět: |
medicine.medical_specialty
Population Hippocampus Rotarod performance test Article Diabetes Mellitus Experimental Cellular and Molecular Neuroscience Glycogen Synthase Kinase 3 Mice GSK-3 Neurotrophic factors Internal medicine Diabetes mellitus medicine Animals Urea Nerve Growth Factors education Maze Learning Cerebral Cortex education.field_of_study biology Recognition Psychology medicine.disease Barnes maze Thiazoles Endocrinology Nerve growth factor Motor Skills Rotarod Performance Test biology.protein Female Psychology Cognition Disorders Neuroscience Neurotrophin |
Zdroj: | Journal of neuroscience research. 91(4) |
ISSN: | 1097-4547 |
Popis: | There is an increasing awareness that diabetes has an impact on the central nervous system, with reports of impaired learning, memory, and mental flexibility being more common in diabetic subjects than in the general population. Insulin-deficient diabetic mice also display learning deficits associated with defective insulin-signaling in the brain and increased activity of GSK3. In the present study, AR-A014418, a GSK3β inhibitor, and TX14(A), a neurotrophic factor with GSK3 inhibitory properties, were tested against the development of learning deficits in mice with insulin-deficient diabetes. Treatments were started at onset of diabetes and continued for 10 weeks. Treatment with AR-A014418 or TX14(A) prevented the development of learning deficits, assessed by the Barnes maze, but only AR-A014418 prevented memory deficits, as assessed by the object recognition test. Diabetes-induced increased levels of amyloid β protein and phosphorylated tau were not significantly affected by the treatments. However, the diabetes-induced decrease in synaptophysin, a presynaptic protein marker of hippocampal plasticity, was partially prevented by both treatments. These results suggest a role for GSK3 and/or reduced neurotrophic support in the development of cognitive deficits in diabetic mice that are associated with synaptic damage. © 2013 Wiley Periodicals, Inc. |
Databáze: | OpenAIRE |
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