Longitudinal evaluation of memory performance and peripheral neuropathy in the Ins2C96Y Akita mice.
Ins2C96Y Akita mice represent a model of spontaneous early-onset diabetes mellitus, expressing a mutant non-functional isoform of insulin. These mice are characterized by a reduced number of pancreatic beta cells resulting in hypoinsulinemia and hyperglycemia. We obtained longitudinal measures of morning fasting blood glucose levels and gait performance. Sciatic nerve electrophysiology was also performed and the performance of these mice on spatial memory tasks was measured longitudinally. We observed a progressive increase in fasting blood glucose levels that was proportionally associated with increased gait disturbances. Diabetes induced a decrease in the sensory nerve conduction velocity up to the age of 40 weeks. Glucose transporter (GLUT) 3 levels were reduced in the hippocampus of the aged Ins2C96Y Akita mice. However, we failed to detect any significant deficits during reference, reversal or probe tests in the Morris water maze or in a spontaneous alternation task up to the age of 34 weeks old. We found that, up to the age of 34 weeks old, uncontrolled hyperglycemia produced peripheral neuropathy and reduced hippocampal GLUT3 levels in the absence of any effect on spatial memory processing.
Choeiri
Cosette
C
School of Psychology, University of Ottawa, 11 Marie Curie, Room 215, Ottawa, Ont., Canada KIN 6N5.
Hewitt
Kimberley
K
Durkin
Jon
J
Simard
Chris J
CJ
Renaud
Jean-Marc
JM
Messier
Claude
C
D000367:Age Factors; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003071:Cognition; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000150:complications / Q000503:physiopathology*; D004195:Disease Models, Animal; D005215:Fasting / Q000097:blood; D005260:Female; D005684:Gait; D051274:Glucose Transporter Type 3; D006624:Hippocampus / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications / Q000503:physiopathology*; D007328:Insulin / Q000172:deficiency / Q000235:genetics; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009431:Neural Conduction; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics; D012584:Sciatic Nerve / Q000503:physiopathology*
D001786:Blood Glucose; D051274:Glucose Transporter Type 3; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C495689:Slc2a3 protein, mouse