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Agmatine protects against intracerebroventricular streptozotocin-induced water maze memory deficit, hippocampal apoptosis and Akt/GSK3β signaling disruption.
Eur J Pharmacol. 2014 Aug 05; 736:107-14.EJ

Abstract

Centrally administered streptozotocin (STZ), is known to cause Alzheimer׳s like memory deterioration. It mainly affects insulin signaling pathways such as PI3/Akt and GSK-3β which are involved in cell survival. Previous studies indicate that STZ increases the ratio of Bax/Bcl-2 and thereby induces caspase-3 activation and apoptosis. Agmatine, a polyamine derived from l-arginine decarboxylation, is recently shown to exert some neuroprotective effects. This study aimed to assess if agmatine reverses STZ-induced memory deficits, hippocampal Akt/GSK-3β signaling disruption and caspase-3 activation. Adult male Sprague-Dawely rats weighing 200-250 g were used. The canules were implanted bilaterally into lateral ventricles. STZ was administered on days 1 and 3 (3 mg/kg) and agmatine treatment (40 or 80 mg/kg) was started from day 4 and continued in an every other day manner till day 14. The animal׳s learning and memory capability was assessed on days 15-18 using Morris water maze. After complement of behavioral studies the hippocampi was isolated and the amounts of hippocampal cleaved caspase-3 (the landmark of apoptosis), Bax/Bcl-2 ratio, total and phosphorylated forms of GSK-3β and Akt were analyzed by western blot. The results showed that agmatine in 80 but not 40 mg/kg reversed the memory deterioration induced by STZ. Western blot analysis revealed that STZ prompted elevation of caspase-3; Bax/Bcl-2 ratio and disrupted Akt/GSK-3β signaling in the hippocampus. Agmatine treatment prevented apoptosis and Akt/GSK-3β signaling impairment induced by STZ. This study disclosed that agmatine treatment averts not only STZ-induced memory deterioration but also hippocampal apoptosis and Akt/GSK-3β signaling disruption.

Authors+Show Affiliations

Department of Physiology and Shiraz Neuroscience Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran; Nanotechnology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: marmoosavi@sums.ac.ir.Department of Physiology and Shiraz Neuroscience Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Physiology, School of Medicine, Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran.Department of Physiology, School of Medicine, Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran. Electronic address: farbood-y@ajums.ac.ir.Department of Physiology, School of Medicine, Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran.Department of Physiology, School of Medicine, Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran.Neuroscience Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Pub Type(s)

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

Language

eng

PubMed ID

24769303

Citation

Moosavi, Maryam, et al. "Agmatine Protects Against Intracerebroventricular Streptozotocin-induced Water Maze Memory Deficit, Hippocampal Apoptosis and Akt/GSK3β Signaling Disruption." European Journal of Pharmacology, vol. 736, 2014, pp. 107-14.
Moosavi M, Zarifkar AH, Farbood Y, et al. Agmatine protects against intracerebroventricular streptozotocin-induced water maze memory deficit, hippocampal apoptosis and Akt/GSK3β signaling disruption. Eur J Pharmacol. 2014;736:107-14.
Moosavi, M., Zarifkar, A. H., Farbood, Y., Dianat, M., Sarkaki, A., & Ghasemi, R. (2014). Agmatine protects against intracerebroventricular streptozotocin-induced water maze memory deficit, hippocampal apoptosis and Akt/GSK3β signaling disruption. European Journal of Pharmacology, 736, 107-14. https://doi.org/10.1016/j.ejphar.2014.03.041
Moosavi M, et al. Agmatine Protects Against Intracerebroventricular Streptozotocin-induced Water Maze Memory Deficit, Hippocampal Apoptosis and Akt/GSK3β Signaling Disruption. Eur J Pharmacol. 2014 Aug 5;736:107-14. PubMed PMID: 24769303.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Agmatine protects against intracerebroventricular streptozotocin-induced water maze memory deficit, hippocampal apoptosis and Akt/GSK3β signaling disruption. AU - Moosavi,Maryam, AU - Zarifkar,Amir Hossein, AU - Farbood,Yaghoub, AU - Dianat,Mahin, AU - Sarkaki,Alireza, AU - Ghasemi,Rasoul, Y1 - 2014/04/23/ PY - 2013/10/25/received PY - 2014/02/13/revised PY - 2014/03/17/accepted PY - 2014/4/29/entrez PY - 2014/4/29/pubmed PY - 2015/2/14/medline KW - Agmatine KW - Akt KW - Apoptosis KW - GSK-3β KW - Learning and memory KW - STZ SP - 107 EP - 14 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 736 N2 - Centrally administered streptozotocin (STZ), is known to cause Alzheimer׳s like memory deterioration. It mainly affects insulin signaling pathways such as PI3/Akt and GSK-3β which are involved in cell survival. Previous studies indicate that STZ increases the ratio of Bax/Bcl-2 and thereby induces caspase-3 activation and apoptosis. Agmatine, a polyamine derived from l-arginine decarboxylation, is recently shown to exert some neuroprotective effects. This study aimed to assess if agmatine reverses STZ-induced memory deficits, hippocampal Akt/GSK-3β signaling disruption and caspase-3 activation. Adult male Sprague-Dawely rats weighing 200-250 g were used. The canules were implanted bilaterally into lateral ventricles. STZ was administered on days 1 and 3 (3 mg/kg) and agmatine treatment (40 or 80 mg/kg) was started from day 4 and continued in an every other day manner till day 14. The animal׳s learning and memory capability was assessed on days 15-18 using Morris water maze. After complement of behavioral studies the hippocampi was isolated and the amounts of hippocampal cleaved caspase-3 (the landmark of apoptosis), Bax/Bcl-2 ratio, total and phosphorylated forms of GSK-3β and Akt were analyzed by western blot. The results showed that agmatine in 80 but not 40 mg/kg reversed the memory deterioration induced by STZ. Western blot analysis revealed that STZ prompted elevation of caspase-3; Bax/Bcl-2 ratio and disrupted Akt/GSK-3β signaling in the hippocampus. Agmatine treatment prevented apoptosis and Akt/GSK-3β signaling impairment induced by STZ. This study disclosed that agmatine treatment averts not only STZ-induced memory deterioration but also hippocampal apoptosis and Akt/GSK-3β signaling disruption. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/24769303/Agmatine_protects_against_intracerebroventricular_streptozotocin_induced_water_maze_memory_deficit_hippocampal_apoptosis_and_Akt/GSK3β_signaling_disruption_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(14)00247-7 DB - PRIME DP - Unbound Medicine ER -