Journal
NEUROPHARMACOLOGY
Volume 85, Issue -, Pages 113-120Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2014.01.036
Keywords
Beta amyloid 25-35; Alzheimer's disease; Morris water maze; Caspase-3; MAPK
Categories
Funding
- Shiraz University of Medical Sciences, Shiraz, Iran [90-5783]
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Alzheimer disease (AD) is a progressive neurodegenerative disease characterized by extracellular deposits of beta amyloid (A beta) 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 A beta-related memory deterioration, hippocampal apoptosis and MAPKs signaling alteration induced by A beta. Adult male Sprague-Dawely rats weighing 250-300 g were used in this study. The canules were implanted bilaterally into CA1 region. A beta 25-35 was administered during first 4 days after surgery (5 mu g/2.5 mu L/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 A beta 25-35. Western blot analysis revealed that A beta 25-35 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 A beta-induced memory deterioration but also hippocampal caspase-3, ERK and P38 activation. (C) 2014 Elsevier Ltd. All rights reserved.
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