Impairment of cognitive flexibility in type 2 diabetic db/db mice
Autor: | Chiho Sugimoto, Leonid M. Yermakov, Michael T. Williams, Domenica E. Drouet, Keiichiro Susuki, Ryan B. Griggs, Charles V. Vorhees |
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Rok vydání: | 2019 |
Předmět: |
Male
medicine.medical_specialty Prefrontal Cortex Morris water navigation task Mice Inbred Strains Water maze Audiology Hippocampus Spatial memory Article Diabetes Mellitus Experimental Executive Function Mice 03 medical and health sciences Behavioral Neuroscience Cognition 0302 clinical medicine Animals Medicine Maze Learning Prefrontal cortex 030304 developmental biology Action potential initiation Memory Disorders 0303 health sciences business.industry Working memory Cognitive flexibility Brain Axon initial segment Disease Models Animal Memory Short-Term Diabetes Mellitus Type 2 Cognition Disorders business 030217 neurology & neurosurgery |
Zdroj: | Behav Brain Res |
ISSN: | 0166-4328 |
Popis: | Impaired executive function is a major peril for patients with type 2 diabetes, reducing quality of life and ability for diabetes management. Despite the significance of this impairment, few animal models of type 2 diabetes examine domains of executive function such as cognitive flexibility or working memory. Here, we evaluated these executive function domains in db/db mice, an established model of type 2 diabetes, at 10 and 24 weeks of age. The db/db mice showed impaired cognitive flexibility in the Morris water maze reversal phase. However, the db/db mice did not show apparent working memory disturbance in the spatial working memory version of the Morris water maze or in the radial water maze. We also examined axon initial segments (AIS) and nodes of Ranvier, key axonal domains for action potential initiation and propagation. AIS were significantly shortened in medial prefrontal cortex and hippocampus of 26-week-old db/db mice compared with controls, similar to our previous findings in 10-week-old mice. Nodes of Ranvier in corpus callosum, previously shown to be unchanged at 10 weeks, were elongated at 26 weeks, suggesting an important role for this domain in disease progression. Together, the findings help establish db/db mice as a model of impaired cognitive flexibility in type 2 diabetes and advance our understanding of its pathophysiology. |
Databáze: | OpenAIRE |
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