Agmatine protects against intracerebroventricular streptozotocin-induced water maze memory deficit, hippocampal apoptosis and Akt/GSK3 beta signaling disruption

作者：Moosavi Maryam^*; Zarifkar Amir Hossein; Farbood Yaghoub; Dianat Mahin; Sarkaki Alireza; Ghasemi Rasoul

来源：European Journal of Pharmacology, 2014, 736: 107-114.

DOI：10.1016/j.ejphar.2014.03.041

• STZ
• Agmatine
• Learning and memory
• Apoptosis
• Akt
• GSK-3 beta

Centrally administered streptozotocin (STZ), is known to cause Alzheimer%26apos;s like memory deterioration. It mainly affects insulin signaling pathways such as PI3/Akt and GSK-3 beta 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-3 beta 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%26apos;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-3 beta 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-3 beta signaling in the hippocampus. Agmatine treatment prevented apoptosis and Akt/GSK-3 beta 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-3 beta signaling disruption.

• 出版日期2014-8-5