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Insulin protects against Aβ-induced spatial memory impairment, hippocampal apoptosis and MAPKs signaling disruption.
Neuropharmacology 2014; 85:113-20N

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+Show Affiliations

Department of Physiology and Shiraz Neuroscience Research Centre, Shiraz University of Medical sciences, Shiraz, Iran.Department of Physiology and Shiraz Neuroscience Research Centre, Shiraz University of Medical sciences, Shiraz, Iran. Electronic address: zarifkara@sums.ac.ir.Department of Physiology and Shiraz Neuroscience Research Centre, Shiraz University of Medical sciences, Shiraz, Iran.Neuroscience Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Department of Physiology and Shiraz Neuroscience Research Centre, Shiraz University of Medical sciences, Shiraz, Iran. Electronic address: mmoosavi2000@gmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24881967

Citation

Ghasemi, Rasoul, et al. "Insulin Protects Against Aβ-induced Spatial Memory Impairment, Hippocampal Apoptosis and MAPKs Signaling Disruption." Neuropharmacology, vol. 85, 2014, pp. 113-20.
Ghasemi R, Zarifkar A, Rastegar K, et al. Insulin protects against Aβ-induced spatial memory impairment, hippocampal apoptosis and MAPKs signaling disruption. Neuropharmacology. 2014;85:113-20.
Ghasemi, R., Zarifkar, A., Rastegar, K., maghsoudi, N., & Moosavi, M. (2014). Insulin protects against Aβ-induced spatial memory impairment, hippocampal apoptosis and MAPKs signaling disruption. Neuropharmacology, 85, pp. 113-20. doi:10.1016/j.neuropharm.2014.01.036.
Ghasemi R, et al. Insulin Protects Against Aβ-induced Spatial Memory Impairment, Hippocampal Apoptosis and MAPKs Signaling Disruption. Neuropharmacology. 2014;85:113-20. PubMed PMID: 24881967.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insulin protects against Aβ-induced spatial memory impairment, hippocampal apoptosis and MAPKs signaling disruption. AU - Ghasemi,Rasoul, AU - Zarifkar,Asadollah, AU - Rastegar,Karim, AU - maghsoudi,Nader, AU - Moosavi,Maryam, Y1 - 2014/06/02/ PY - 2013/09/27/received PY - 2014/01/15/revised PY - 2014/01/21/accepted PY - 2014/6/3/entrez PY - 2014/6/3/pubmed PY - 2015/3/31/medline KW - Alzheimer's disease KW - Beta amyloid 25-35 KW - Caspase-3 KW - MAPK KW - Morris water maze SP - 113 EP - 20 JF - Neuropharmacology JO - Neuropharmacology VL - 85 N2 - 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. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/24881967/Insulin_protects_against_Aβ_induced_spatial_memory_impairment_hippocampal_apoptosis_and_MAPKs_signaling_disruption_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(14)00043-4 DB - PRIME DP - Unbound Medicine ER -