Amyloid-beta(25-35)-induced memory impairments correlate with cell loss in rat hippocampus.
Amyloid beta-peptide (Abeta) plays an important role in the pathophysiology of Alzheimer's disease. The relationship between amnesia induced by central administration of aggregated Abeta(25-35) and neurodegeneration in the hippocampus was investigated. One month after a single intracerebroventricular injection of Abeta(25-35) (15 nmol), male Wistar rats were tested in an eight-arm radial maze. A quantitative evaluation of cell number in hippocampal regions was carried out on H&E-stained brain sections of rats used in the behavioral study. Indices of free radical-mediated processes in the hippocampus were evaluated in additional groups of animals 1, 3, 5, and 30 days after surgery. Abeta(25-35) induced impairments of working and reference memory (RM) as well as neurodegeneration in the CA1 but not in the CA3 field of the hippocampus. A significant correlation between both reference and working memory (WM) impairments and the neuronal cell loss in the hippocampal CA1 region was demonstrated. A gradually developing oxidative stress was evident in the hippocampus of rats treated with Abeta(25-35) as indicated by the increase in 2-thiobarbituric acid (TBARS) reactive substances and superoxide generation. These data suggest the involvement of oxidative stress in Abeta(25-35)-induced neurodegeneration and a relation between memory impairment and neurodegeneration in the CA1 subfield of the hippocampus.
Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 5a Butlerov Str., Moscow 117485, Russia.
Mikhail Yu
MY
Stepanichev
Irina M
IM
Zdobnova
Irina I
II
Zarubenko
Yulia V
YV
Moiseeva
Natalia A
NA
Lazareva
Mikhail V
MV
Onufriev
Natalia V
NV
Gulyaeva
D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D016923:Cell Death; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35)