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Melanocortins protect against brain damage and counteract cognitive decline in a transgenic mouse model of moderate Alzheimer׳s disease.
Giuliani, Daniela; Galantucci, Maria; Neri, Laura; Canalini, Fabrizio; Calevro, Anita; Bitto, Alessandra; Ottani, Alessandra; Vandini, Eleonora; Sena, Paola; Sandrini, Maurizio; Squadrito, Francesco; Zaffe, Davide; Guarini, Salvatore.
Afiliação
  • Giuliani D; Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: daniela.giuliani@unimore.it.
  • Galantucci M; Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Modena, Italy.
  • Neri L; Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Modena, Italy.
  • Canalini F; Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Modena, Italy.
  • Calevro A; Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Modena, Italy.
  • Bitto A; Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Messina, Messina, Italy.
  • Ottani A; Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Modena, Italy.
  • Vandini E; Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Modena, Italy.
  • Sena P; Department of Biomedical, Metabolic and Neural Sciences, Section of Human Morphology, University of Modena and Reggio Emilia, Modena, Italy.
  • Sandrini M; Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Modena, Italy.
  • Squadrito F; Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Messina, Messina, Italy.
  • Zaffe D; Department of Biomedical, Metabolic and Neural Sciences, Section of Human Morphology, University of Modena and Reggio Emilia, Modena, Italy.
  • Guarini S; Department of Biomedical, Metabolic and Neural Sciences, Section of Pharmacology and Molecular Medicine, University of Modena and Reggio Emilia, Modena, Italy. Electronic address: salvatore.guarini@unimore.it.
Eur J Pharmacol ; 740: 144-50, 2014 Oct 05.
Article em En | MEDLINE | ID: mdl-25034807
ABSTRACT
We previously reported that melanocortins induce neuroprotection in experimental acute and chronic neurodegenerative conditions, including Alzheimer׳s disease (AD) of mild severity. Here we investigated whether melanocortins afford neuroprotection and counteract cognitive decline in AD with a medium level of severity by using 24 week-old (at the start of the study) APPSwe transgenic mice (Tg2576). Saline-treated (days 1-50) control Tg2576 mice showed an impairment in spatial learning and memory, associated (at day 50, end of the study) with hippocampus at low levels of the synaptic activity-dependent gene Zif268, relevant brain changes such as cerebral cortex/hippocampus increased level of ß-amyloid (Aß) deposit, and neuronal loss, in comparison with wild-type animals. Treatment of Tg2576 mice (once daily at days 1-50) with a nanomolar dose of the melanocortin analog [Nle4,D-Phe7]α-melanocyte-stimulating hormone (NDP-α-MSH) reduced cerebral cortex/hippocampus level of Aß deposit, decreased neuronal loss, increased hippocampus Zif268 expression and improved cognitive functions, relative to saline-treated Tg2576 mice. Pharmacological blockade of melanocortin MC4 receptors with the MC4 receptor antagonist HS024 prevented all favorable effects of NDP-α-MSH. Our data indicate that MC4 receptor-stimulating melanocortins are able to counteract cognitive decline in experimental AD of medium severity through induction of neuroprotection and improvement of synaptic transmission. After further studies, these agents could gain a role as disease modifying therapeutics for AD.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Alfa-MSH / Transtornos Cognitivos / Fármacos Neuroprotetores / Doença de Alzheimer Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Alfa-MSH / Transtornos Cognitivos / Fármacos Neuroprotetores / Doença de Alzheimer Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article