title: Repeated intra-hippocampal injection of beta-amyloid 25–35 induces a reproducible impairment of learning and memory: considering caspase-3 and MAPKs activity.
abstract: Alzheimer disease (AD) is characterized by accumulation of beta amyloid (Aβ) and neuronal loss, particularly in the hippocampus. Direct central administration of this peptide was suggested as a route to create an animal model of AD. Although there are some studies indicating that a single dose of Aβ induces AD-like learning and memory impairment, this model is not usually reproducible especially in rat. Then one of the aims of this study was to explore a more reliable method to trigger AD-like behavioral impairments in rat through a series of pilot studies. In other step, according to some controversies about roles of MAPKs (P38, JNK and ERK) in AD, these kinases were assayed in beta amyloid-treated rats with or without memory impairment. A series of pilot studies was done to assess if a single Aβ injection (5, 10, 15 µg/each side) induces reproducible memory impairment. Because of the failure of that set of studies, another set of experiment with repeated Aβ administration during four days was carried out. The results showed that in contrast to single treatment of beta amyloid, its repeated administration (5 µg/2.5 µl each side/day) during 4 days led to memory deterioration. Hippocampal western blot analysis revealed that behavioral impairment is in parallel with greater apoptosis and MAPKs activation. This study introduces a new method for inducing AD models by repeated intra-CA1 injection of Aβ25–35. Additionally it elucidates how caspase-3 and MAPKs activity differ between beta amyloid-treated rats with or without learning and memory impairment.
authors.forename: Rasoul
authors.initials: R
authors.lastname: Ghasemi
authors.forename: Asadollah
authors.initials: A
authors.lastname: Zarifkar
authors.forename: Karim
authors.initials: K
authors.lastname: Rastegar
authors.forename: Nader
authors.initials: N
authors.lastname: Maghsoudi
authors.forename: Maryam
authors.initials: M
authors.lastname: Moosavi
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D065853:Spatial Learning / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3