Intrahippocampal administration of Aβ1-40 impairs spatial learning and memory in hyperglycemic mice
Journal
Neurobiology of Learning and Memory
Journal Volume
87
Journal Issue
4
Pages
483-494
Date Issued
2007
Author(s)
Abstract
Age-related neurodegenerative dementia, particularly Alzheimer's disease (AD), may be exacerbated by several interacting risk factors including genetic predisposition, beta amyloid (Aβ) protein accumulation, environmental toxins, head trauma, and abnormal glycolytic metabolism. We examined the spatial learning and memory effects of Aβ1-40 administration on hyperglycemic mice by their performance in the Morris water maze. Chronic hyperglycemia was induced in male C57BL/6J mice to mimic diabetes mellitus by intraperitoneal injection of streptozotocin (STZ), which specifically destroys pancreatic β-islet cells. Ten days after STZ treatment, intrahippocampal infusion of vehicle, monomer, or oligomer Aβ1-40 was given to these hyperglycemic mice. Our results demonstrate that in comparison with vehicle or monomer Aβ1-40, oligomer Aβ1-40 induced significant deficits of spatial learning and memory in hyperglycemic mice. Apoptotic signals were identified in the CA1 and dentate gyrus of hippocampus in hyperglycemic mice. Aβ accumulation, oxidative stress, and apoptosis in the CA1 region were more intensive in hyperglycemic mice than that in normoglycemic mice after acute treatment with oligomer Aβ1-40 peptide treatment. These results indicate that CA1 apoptosis was enhanced by oxidative stress resulting from accumulation of Aβ. Considered together, these findings suggest that hyperglycemic mice are more vulnerable to the Aβ-induced-oxidative stress than normal subjects. We therefore propose that Aβ accumulation would be enhanced by hyperglycemia, and the oxidative stress caused by Aβ accumulation would in turn enhance the AD symptoms. ? 2006 Elsevier Inc. All rights reserved.
Subjects
β-Amyloid; Alzheimer's disease; Diabetes mellitus; Hippocampus; Spatial reference memory; Streptozotocin
SDGs
Other Subjects
amyloid beta protein[1-40]; drug vehicle; monomer; oligomer; streptozocin; Alzheimer disease; animal experiment; animal model; animal tissue; apoptosis; article; controlled study; dentate gyrus; hippocampus; hyperglycemia; learning disorder; male; maze test; memory disorder; mouse; nonhuman; oxidative stress; pancreas islet beta cell; streptozocin diabetes; task performance; Amyloid beta-Protein; Analysis of Variance; Animals; Apoptosis; Blood Glucose; Diabetes Mellitus, Experimental; Discrimination Learning; Hippocampus; Hyperglycemia; Male; Maze Learning; Mice; Mice, Inbred C57BL; Microinjections; Neurons; Peptide Fragments; Spatial Behavior
Type
journal article