Memory impairment in obese Zucker rats: an investigation of cognitive function in an animal model of insulin resistance and obesity.
The genetically obese Zucker rat is a widely investigated model of pathological changes associated with type 2 diabetes. To assess cognitive function, obese and lean Zucker rats were tested on a variable-interval delayed alternation test of learning and memory. There were no group differences in learning the alternation rule or at short intervals, but obese rats were impaired at longer intervals where performance is hippocampus dependent. Plasma membrane association of the insulin sensitive glucose transporter, GLUT4, was reduced in the hippocampus of obese rats in the absence of changes in total GLUT4 and insulin receptor expression. These results parallel those of human studies in pointing to the susceptibility of the hippocampus and related structures to the adverse environment of diabetes mellitus.
Winocur
Gordon
G
Department of Psychology, Trent University, Peterborough, Ontario, Canada. gwinocur@rotman-baycrest.on.ca
Greenwood
Carol E
CE
Piroli
Gerardo G
GG
Grillo
Claudia A
CA
Reznikov
Leah R
LR
Reagan
Lawrence P
LP
McEwen
Bruce S
BS
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001786:Blood Glucose; D015153:Blotting, Western / Q000379:methods; D002462:Cell Membrane / Q000378:metabolism; D002755:Choice Behavior / Q000502:physiology; D003071:Cognition / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D007333:Insulin Resistance / Q000502:physiology*; D008569:Memory Disorders / Q000378:metabolism / Q000503:physiopathology*; D009765:Obesity / Q000503:physiopathology*; D011597:Psychomotor Performance; D051381:Rats; D011924:Rats, Zucker; D011972:Receptor, Insulin / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D012055:Reinforcement Schedule; D013997:Time Factors
D001786:Blood Glucose; D018091:Receptors, AMPA; C104724:glutamate receptor ionotropic, AMPA 4; D011972:Receptor, Insulin