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CEPO-Fc (An EPO Derivative) Protects Hippocampus Against Aβ-induced Memory Deterioration: A Behavioral and Molecular Study in a Rat Model of Aβ Toxicity.
Neuroscience. 2018 09 15; 388:405-417.N

Abstract

Alzheimer's disease (AD) is a debilitating neurodegenerative disease, characterized by extracellular deposition of senile plaques, mostly amyloid β-protein (Aβ) and neuronal loss. The neuroprotective effects of erythropoietin (EPO) have been reported in some models of neurodegenerative disease, but because of its hematopoietic side effects, its derivatives lacking hematopoietic bioactivity is recommended. In this study, the neuroprotective effects of carbamylated erythropoietin-Fc (CEPO-Fc) against beta amyloid-induced memory deficit were evaluated. Adult male Wistar rats weighing 250-300 g were bilaterally cannulated into CA1. Aβ25-35 was administered intrahippocampally for 4 consecutive days (5 μg/2.5 μL/each side/day). CEPO-Fc (500 or 5000 IU) was injected intraperitoneally during days 4-9. Learning and memory performance of rats was assessed on days 10-13 using Morris Water Maze, then hippocampi were isolated and the amount of activated forms of hippocampal MAPKs' subfamily, Akt/GSK-3β and MMP-2 were analyzed using Western blot. From the behavioral results, it was revealed that CEPO-Fc treatment in both 500 and 5000 IU significantly reversed Aβ-induced learning and memory deterioration. From the molecular analysis, an increment of MAPKs and MMP-2 activity and an imbalance in Akt/GSK-3β signaling after Aβ25-35 administration was observed. CEPO-Fc treatment prevented the elevation of hippocampal of P38, ERK, MMP-2 activity and also Akt/GSK-3β signaling impairment induced by Aβ25-35 but it had no effect on JNK. It seems that CEPO-Fc prevents Aβ-induced learning and memory deterioration, and also modulates hippocampal MAPKs, Akt/GSK-3β and MMP-2 activity. This study suggests that CEPO-Fc can be considered as a potential therapeutic strategy for memory deficits like AD.

Authors+Show Affiliations

Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Nanobiology and Nanomedicine Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran; Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.Department of Biology, Queens College and Graduate Center of the City University of New York, Flushing, NY, USA.Neurophysiology Research Center and Physiology Department, Shahid Beheshti University of Medical Sciences, Tehran, Iran.R&D Unit, Humer Novin Daroo Tolid Co., Tehran, Iran.Neurophysiology Research Center and Physiology Department, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: rghasemi60@sbmu.ac.ir.Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Biology, Queens College and Graduate Center of the City University of New York, Flushing, NY, USA; Neurobiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: Nmaghsoudi@sbmu.ac.ir.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30102955

Citation

Hooshmandi, Etrat, et al. "CEPO-Fc (An EPO Derivative) Protects Hippocampus Against Aβ-induced Memory Deterioration: a Behavioral and Molecular Study in a Rat Model of Aβ Toxicity." Neuroscience, vol. 388, 2018, pp. 405-417.
Hooshmandi E, Motamedi F, Moosavi M, et al. CEPO-Fc (An EPO Derivative) Protects Hippocampus Against Aβ-induced Memory Deterioration: A Behavioral and Molecular Study in a Rat Model of Aβ Toxicity. Neuroscience. 2018;388:405-417.
Hooshmandi, E., Motamedi, F., Moosavi, M., Katinger, H., Zakeri, Z., Zaringhalam, J., Maghsoudi, A., Ghasemi, R., & Maghsoudi, N. (2018). CEPO-Fc (An EPO Derivative) Protects Hippocampus Against Aβ-induced Memory Deterioration: A Behavioral and Molecular Study in a Rat Model of Aβ Toxicity. Neuroscience, 388, 405-417. https://doi.org/10.1016/j.neuroscience.2018.08.001
Hooshmandi E, et al. CEPO-Fc (An EPO Derivative) Protects Hippocampus Against Aβ-induced Memory Deterioration: a Behavioral and Molecular Study in a Rat Model of Aβ Toxicity. Neuroscience. 2018 09 15;388:405-417. PubMed PMID: 30102955.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CEPO-Fc (An EPO Derivative) Protects Hippocampus Against Aβ-induced Memory Deterioration: A Behavioral and Molecular Study in a Rat Model of Aβ Toxicity. AU - Hooshmandi,Etrat, AU - Motamedi,Fereshteh, AU - Moosavi,Maryam, AU - Katinger,Hermann, AU - Zakeri,Zahra, AU - Zaringhalam,Jalal, AU - Maghsoudi,Amirhossein, AU - Ghasemi,Rasoul, AU - Maghsoudi,Nader, Y1 - 2018/08/11/ PY - 2018/04/18/received PY - 2018/07/02/revised PY - 2018/08/02/accepted PY - 2018/8/14/pubmed PY - 2019/3/30/medline PY - 2018/8/14/entrez KW - Akt/GSK-3β KW - Alzheimer’s disease KW - CEPO-Fc KW - MAPKs KW - MMP-2 SP - 405 EP - 417 JF - Neuroscience JO - Neuroscience VL - 388 N2 - Alzheimer's disease (AD) is a debilitating neurodegenerative disease, characterized by extracellular deposition of senile plaques, mostly amyloid β-protein (Aβ) and neuronal loss. The neuroprotective effects of erythropoietin (EPO) have been reported in some models of neurodegenerative disease, but because of its hematopoietic side effects, its derivatives lacking hematopoietic bioactivity is recommended. In this study, the neuroprotective effects of carbamylated erythropoietin-Fc (CEPO-Fc) against beta amyloid-induced memory deficit were evaluated. Adult male Wistar rats weighing 250-300 g were bilaterally cannulated into CA1. Aβ25-35 was administered intrahippocampally for 4 consecutive days (5 μg/2.5 μL/each side/day). CEPO-Fc (500 or 5000 IU) was injected intraperitoneally during days 4-9. Learning and memory performance of rats was assessed on days 10-13 using Morris Water Maze, then hippocampi were isolated and the amount of activated forms of hippocampal MAPKs' subfamily, Akt/GSK-3β and MMP-2 were analyzed using Western blot. From the behavioral results, it was revealed that CEPO-Fc treatment in both 500 and 5000 IU significantly reversed Aβ-induced learning and memory deterioration. From the molecular analysis, an increment of MAPKs and MMP-2 activity and an imbalance in Akt/GSK-3β signaling after Aβ25-35 administration was observed. CEPO-Fc treatment prevented the elevation of hippocampal of P38, ERK, MMP-2 activity and also Akt/GSK-3β signaling impairment induced by Aβ25-35 but it had no effect on JNK. It seems that CEPO-Fc prevents Aβ-induced learning and memory deterioration, and also modulates hippocampal MAPKs, Akt/GSK-3β and MMP-2 activity. This study suggests that CEPO-Fc can be considered as a potential therapeutic strategy for memory deficits like AD. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/30102955/CEPO_Fc__An_EPO_Derivative__Protects_Hippocampus_Against_Aβ_induced_Memory_Deterioration:_A_Behavioral_and_Molecular_Study_in_a_Rat_Model_of_Aβ_Toxicity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(18)30539-6 DB - PRIME DP - Unbound Medicine ER -