黑素皮质素
黑皮素
神经保护
冲程(发动机)
医学
海马体
海马结构
缺血
药理学
内科学
内分泌学
神经科学
受体
心理学
机械工程
工程类
作者
Daniela Giuliani,Alessandra Ottani,Letteria Minutoli,Vincenzo Di Stefano,Maria Galantucci,Alessandra Bitto,Davide Zaffe,Domenica Altavilla,A Botticelli,Francesco Squadrito,Salvatore Guarini
标识
DOI:10.1016/j.bbi.2009.03.009
摘要
Melanocortin peptides afford strong neuroprotection and improve functional recovery in experimental ischemic stroke; they also have established neurotrophic actions. The expression of the immediate early gene Zif268 is dependent on synaptic activity and is involved in injury repair and memory formation. Here, we investigated the role of Zif268 in learning and memory recovery after delayed treatment of ischemic stroke with the melanocortin analog [Nle(4), D-Phe(7)]alpha-MSH (NDP-alpha-MSH). A 10-min period of global cerebral ischemia was induced by occluding both common carotid arteries in gerbils. Treatment with a nanomolar dose of NDP-alpha-MSH (every 12h for 11 days) was performed starting 3h or 9h after stroke induction; where indicated, gerbils were pretreated with the melanocortin MC(4) receptor antagonist HS024. Animals were subjected to the Morris water-maze test (four sessions from 4 to 50 days after the ischemic episode). Fifty days after stroke, histological damage and Zif268 expression were investigated in the hippocampus. Treatment with NDP-alpha-MSH significantly reduced hippocampal damage, including neuronal death, and improved learning and memory recovery. This protective effect was long-lasting (50 days, at least) and associated with Zif268 overexpression, with both schedules of NDP-alpha-MSH treatment. Pharmacological blockade of MC(4) receptors prevented these effects. Our data indicate that MC(4) receptor-mediated actions of melanocortins could trigger repair mechanisms able to improve neuronal functionality and synaptic plasticity, and to promote long-lasting functional recovery from ischemic stroke with Zif268 gene involvement.
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