title: Insulin protects against Aβ-induced spatial memory impairment, hippocampal apoptosis and MAPKs signaling disruption.
abstract: Alzheimer disease (AD) is a progressive neurodegenerative disease characterized by extracellular deposits of beta amyloid (Aβ) and neuronal loss particularly in the hippocampus. Accumulating evidences have implied that insulin signaling impairment plays a key role in the pathology of AD; as much as it is considered as type 3 Diabetes. MAPKs are a group of signaling molecules which are involved in pathobiology of AD. Therefore this study was designed to investigate if intrahippocampal insulin hinders Aβ-related memory deterioration, hippocampal apoptosis and MAPKs signaling alteration induced by Aβ. Adult male Sprague-Dawely rats weighing 250-300 g were used in this study. The canules were implanted bilaterally into CA1 region. Aβ25-35 was administered during first 4 days after surgery (5 μg/2.5 μL/daily). Insulin treatment (0.5 or 6 mU) was done during days 4-9. The animal's learning and memory capability was assessed on days 10-13 using Morris water maze. After finishing of behavioral studies the hippocampi was isolated and the amount of hippocampal cleaved caspase 3 (the landmark of apoptosis) and the phosphorylated (activated) forms of P38, JNK and ERK was analyzed by western blot. The results showed that insulin in 6 but not 0.5 mU reversed the memory loss induced by Aβ25-35. Western blot analysis revealed that Aβ25-35 induced elevation of caspase-3 and all 3 MAPks subfamily activity, while insulin in 6 mu restored ERK and P38 activation but has no effect on JNK. This study disclosed that intrahippocampal insulin treatment averts not only Aβ-induced memory deterioration but also hippocampal caspase-3, ERK and P38 activation.
authors.affiliation: Department of Physiology and Shiraz Neuroscience Research Centre, Shiraz University of Medical sciences, Shiraz, Iran.
authors.forename: Rasoul
authors.initials: R
authors.lastname: Ghasemi
authors.affiliation: Department of Physiology and Shiraz Neuroscience Research Centre, Shiraz University of Medical sciences, Shiraz, Iran. Electronic address: zarifkara@sums.ac.ir.
authors.forename: Asadollah
authors.initials: A
authors.lastname: Zarifkar
authors.affiliation: Department of Physiology and Shiraz Neuroscience Research Centre, Shiraz University of Medical sciences, Shiraz, Iran.
authors.forename: Karim
authors.initials: K
authors.lastname: Rastegar
authors.affiliation: Neuroscience Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Nader
authors.initials: N
authors.lastname: maghsoudi
authors.affiliation: Department of Physiology and Shiraz Neuroscience Research Centre, Shiraz University of Medical sciences, Shiraz, Iran. Electronic address: mmoosavi2000@gmail.com.
authors.forename: Maryam
authors.initials: M
authors.lastname: Moosavi
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D007328:Insulin; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: Alzheimer's disease; Beta amyloid 25-35; Caspase-3; MAPK; Morris water maze