Neurochemical and behavioral effects of the intrahippocampal co-injection of beta-amyloid protein1-40 and ibotenic acid in rats.
The present study was designed to investigate the effects of the intrahippocampal co-injection of beta-amyloid protein1-40 (Abeta(1-40)) with ibotenic acid (Ibo) on learning and memory in normal and aging model rats, and to explore the mechanism underlying the effects of the co-injection. The normal and aging rats were bilaterally injected Abeta(1-40) (4 microg for each side) with Ibo (2 microg for each side) into the hippocampus. Two weeks after the intrahippocampal injection, the exploratory behavior and learning-memory ability of the rats were tested by using open field, Y-maze and passive avoidance task. And the changes of membrane fluidity in hippocampal mitochondria, the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in hippocampus were also examined. The co-injection of Abeta(1-40) with Ibo induced tested rats a remarkable decrease in the explorative behaviors and a significant decline in learning-memory ability (P < 0.01). The neurochemical changes induced by the co-injection included a significant decrease in membrane fluidity of hippocampal mitochondria (P < 0.01), a significant decrease in the activity of SOD (P < 0.01), as well as a remarkable increase in the content of MDA (P < 0.01). The results suggest that co-injection of Abeta(1-40) with Ibo may induce an increase of hippocampal damage by peroxidation and a serious deficit in the learning and memory of the rats. The results also suggest that the co-injection of Abeta(1-40) with Ibo may provide a useful animal model for the Alzheimer's disease (AD) research.
Li
Ya
Y
Department of Biological Science and Technology and State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Mailbox 426, Nanjing University, 22 Hankou Road, Nanjing 210093, China.
Qin
Hai-Qiang
HQ
Chen
Qi-Sheng
QS
Wang
Jian-Jun
JJ
D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D004357:Drug Synergism; D005106:Exploratory Behavior / Q000187:drug effects; D005690:Galactose / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007051:Ibotenic Acid / Q000633:toxicity*; D007267:Injections; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008560:Membrane Fluidity / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D023421:Models, Animal; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D007051:Ibotenic Acid; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D005690:Galactose