ABSTRACT
The effects of intracerebroventricular administration of fragment (25-35) of beta-amyloid peptide [Abeta(25-35)] on cell proliferation in the subventricular zone of the dentate gyrus of the hippocampus in adult rats were analyzed. Animals received doses of 15 nmol of pre-aggregated Abeta(25-35) or the Abeta(35-25) control peptide, or solvent (sterile water) into the lateral ventricles. On post-injection days 1-5, rats received intraperitoneal injections of the thymidine analog 5-bromo-2'-deoxyuridine (BrdU). BrdU incorporated into DNA was detected immunohistochemically on frontal brain sections six and 12 days after peptide administration. At six days, the numbers of BrdU-containing cells in the subventricular zone showed no differences between the study groups. At 12 days, the total number of BrdU-positive cells decreased significantly in all study groups. At the same time, the number of labeled cells in rats given Abeta(25-35) was significantly greater in this brain zone than in animals given water or the control peptide. Thus, Abeta(25-35) significantly increased cell proliferation in the subventricular zone after intracerebroventricular administration.
Subject(s)
Amyloid beta-Peptides/metabolism , Cell Proliferation , Dentate Gyrus/physiology , Peptide Fragments/metabolism , Stem Cell Niche/physiology , Aging , Animals , Bromodeoxyuridine , Immunohistochemistry , Male , Protein Multimerization , Rats , Rats, Wistar , Time FactorsABSTRACT
Decreases in cognitive functions, particularly long-term (episodic) and working memory, are among the earliest prognostic signs of Alzheimer's disease. The toxicity of beta-amyloid peptide is regarded as a major cause of neurodegeneration and cognitive impairment in this disease. The present report describes studies of the effects of intracerebroventricular administration of beta-amyloid peptide (25-35) (Abeta(25-35)) on the reproduction of a previously assimilated habit consisting of finding food in an eight-arm radial maze in rats. Abeta(25-35) was given bilaterally at doses of 15 and 30 nmol/animal seven days after preliminary training. Testing was performed 60 days after peptide administration. The results showed that Abeta(25-35) impaired working memory in rats without having any significant effect on the retention of responses. We were unable to demonstrate any relationship between memory impairment and the dose of peptide given. These data provide evidence of the ability of Abeta(25-35) to produce greater degradation of working memory function than long-term memory function.
Subject(s)
Amyloid beta-Peptides/pharmacology , Behavior, Animal/drug effects , Maze Learning/drug effects , Peptide Fragments/pharmacology , Animals , Dose-Response Relationship, Drug , Functional Laterality/drug effects , Injections, Intraventricular/methods , Male , Rats , Rats, Wistar , Reaction Time/drug effects , Retention, Psychology/drug effects , Time FactorsABSTRACT
Ample experimental evidence indicates that intracerebral injection or infusion of amyloid-beta peptides (Abeta) to rodents induces learning and memory impairments as well as neurodegeneration in brain areas related to cognitive function. In the present study, we assessed the effects of a single intracerebroventricular (i.c.v.) injection of aggregated Abeta fragment (25-35) at a dose of 15nmol/rat on short-term and long-term memory in rats during the 6-month post-surgery period. The results demonstrate that Abeta(25-35)-induced memory impairments in spontaneous alternation behavior in a Y-maze at 17, 36, and 180 days after the surgery as well as in a social recognition task 110 days post-surgery. Abeta(25-35) also impaired spatial memory in an 8-arm radial maze, but did not influence performance of the step-down passive avoidance task. These results suggest that Abeta(25-35) preferably induces impairments of spatial and non-spatial short-term (working) memory rather than long-term memory in rats.
