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 [Nle4, d-Phe7]α-MSH (NDP-α-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-α-MSH (every 12 h for 11 days) was performed starting 3 h or 9 h after stroke induction; where indicated, gerbils were pretreated with the melanocortin MC4 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-α-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-α-MSH treatment. Pharmacological blockade of MC4 receptors prevented these effects. Our data indicate that MC4 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.

Functional recovery after delayed treatment of ischemic stroke with melanocortins is associated with overexpression of the activity-dependent gene Zif268 / Giuliani, Daniela; Ottani, Alessandra; Letteria, Minutoli; Vincenzo Di, Stefano; Maria, Galantucci; Alessandra, Bitto; Zaffe, Davide; Domenica, Altavilla; Annibale R., Botticelli; Francesco, Squadrito; Guarini, Salvatore. - In: BRAIN BEHAVIOR AND IMMUNITY. - ISSN 0889-1591. - STAMPA. - 23:6(2009), pp. 844-850. [10.1016/j.bbi.2009.03.009]

Functional recovery after delayed treatment of ischemic stroke with melanocortins is associated with overexpression of the activity-dependent gene Zif268

GIULIANI, Daniela;OTTANI, Alessandra;ZAFFE, Davide;GUARINI, Salvatore
2009

Abstract

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 [Nle4, d-Phe7]α-MSH (NDP-α-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-α-MSH (every 12 h for 11 days) was performed starting 3 h or 9 h after stroke induction; where indicated, gerbils were pretreated with the melanocortin MC4 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-α-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-α-MSH treatment. Pharmacological blockade of MC4 receptors prevented these effects. Our data indicate that MC4 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.
2009
23
6
844
850
Functional recovery after delayed treatment of ischemic stroke with melanocortins is associated with overexpression of the activity-dependent gene Zif268 / Giuliani, Daniela; Ottani, Alessandra; Letteria, Minutoli; Vincenzo Di, Stefano; Maria, Galantucci; Alessandra, Bitto; Zaffe, Davide; Domenica, Altavilla; Annibale R., Botticelli; Francesco, Squadrito; Guarini, Salvatore. - In: BRAIN BEHAVIOR AND IMMUNITY. - ISSN 0889-1591. - STAMPA. - 23:6(2009), pp. 844-850. [10.1016/j.bbi.2009.03.009]
Giuliani, Daniela; Ottani, Alessandra; Letteria, Minutoli; Vincenzo Di, Stefano; Maria, Galantucci; Alessandra, Bitto; Zaffe, Davide; Domenica, Altavilla; Annibale R., Botticelli; Francesco, Squadrito; Guarini, Salvatore
File in questo prodotto:
File Dimensione Formato  
BBI zif 2009.pdf

Solo gestori archivio

Tipologia: Versione pubblicata dall'editore
Dimensione 544.05 kB
Formato Adobe PDF
544.05 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/639542
Citazioni
  • ???jsp.display-item.citation.pmc??? 7
  • Scopus 32
  • ???jsp.display-item.citation.isi??? 31
social impact