Differential effects of tumor necrosis factor-alpha co-administered with amyloid beta-peptide (25-35) on memory function and hippocampal damage in rat.
Effects of concurrent intracerebroventricular administration of amyloid-beta peptide 25-35 (Abeta(25-35)) and the proinflammatory cytokine tumor necrosis factor-alpha (TNFalpha) to rats were investigated. A battery of behavioral tests including radial arm maze, passive avoidance, elevated plus-maze and forced swim test as well as histological methods were used. A single administration of Abeta(25-35) induced delayed behavioral deficits manifested in reference and working memory disturbances in the radial maze task involving spatial memory. However, no effects of Abeta(25-35) on learning or retention in a passive avoidance test could be revealed. Abeta(25-35) appeared to decrease anxiety without affecting depression-like behavior in the rats. Abeta(25-35)-induced cognitive deficits could be related to the moderate neuronal cell loss found in the hippocampal CA1 field. Though administration of TNFalpha did not impair learning and memory of rats in the radial maze, it induced gross changes in their behavior during passive avoidance training. Though TNFalpha did not protect against Abeta(25-35)-induced neuronal cell loss in the CA1 field of hippocampus, co-administration of TNFalpha with Abeta(25-35) resulted in an improvement of reference memory impaired by the amyloid peptide, but not of working memory.
Stepanichev
Mikhail
M
Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 5a Butlerov Street, Moscow 117485, Russia.
Zdobnova
Irina
I
Zarubenko
Irina
I
Lazareva
Natalia
N
Gulyaeva
Natalia V
NV
D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000502:physiology; D006624:Hippocampus / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C074636:amyloid beta-protein (25-35)