Beta-amyloid(1-40)-induced neurodegeneration in the rat hippocampal neurons of the CA1 subfield.
Small volumes of solutions injected into the hippocampus produce dramatic degeneration in dentate gyrus neurons, but not in neurons of the CA1 subfield. The aim of the present study was to ascertain whether solutions with different fragments of the beta-amyloid protein (Abeta) could produce further degeneration in areas beyond the dentate gyrus. It was found that 5 days after injection of an aqueous solution containing the Abeta 1-40 fragment into the hippocampus, long stretches of the CA1 subfield were either deprived of neurons or most of the neurons were degenerating. By contrast, in animals with deposits containing Abeta 1-28, Abeta 1-42 or water, neuronal degeneration or depletion only occurred in a reduced area around the place where the implant needle penetrated the CA1 subfield. In animals injected with Abeta 1-40, many profiles in the CA1 subfield and dentate gyrus were undergoing apoptosis, as seen using preparations processed by routine histology or the TUNEL technique for detection of fragmented DNA. In addition, there was higher infiltration by ED1-positive, activated microglia-macrophagic cells in Abeta 1-42 deposits than in deposits of Abeta 1-40. The present results suggest that the intrahippocampal injection of toxic Abeta fragments produces neuronal degeneration in the rat CA1 subfield when using the appropriate protocol, and, thus, can provide an in vivo model to investigate the neurotoxic effects of Abeta and for the evaluation of drugs with potential anti-neurodegenerative activity.
Miguel-Hidalgo
J J
JJ
Department of Basic Neuroscience, EuroEspes Biomedical Research Center, Santa Marta de Babío, Bergondo, La Coruña, Spain. euroespes@lcg.servicom.es
Cacabelos
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D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry; D008264:Macrophages / Q000187:drug effects; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C084358:amyloid beta-protein (1-28); C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)