Agmatine protects against intracerebroventricular streptozotocin-induced water maze memory deficit, hippocampal apoptosis and Akt/GSK3β signaling disruption.
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.
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.
Maryam
M
Moosavi
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.
Amir Hossein
AH
Zarifkar
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.
Yaghoub
Y
Farbood
Department of Physiology, School of Medicine, Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran.
Mahin
M
Dianat
Department of Physiology, School of Medicine, Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran.
Alireza
A
Sarkaki
Neuroscience Research Centre, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Rasoul
R
Ghasemi
D000376:Agmatine / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D057967:Infusions, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin / Q000008:administration & dosage / Q000009:adverse effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D013311:Streptozocin; D000376:Agmatine; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; C505410:Casp3 protein, rat; D053148:Caspase 3
Agmatine; Akt; Apoptosis; GSK-3β; Learning and memory; STZ