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Protective effect of neuropeptide Y2 receptor activation against methamphetamine-induced brain endothelial cell alterations.
Ventura, Fabiana; Muga, Mariana; Coelho-Santos, Vanessa; Fontes-Ribeiro, Carlos A; Leitão, Ricardo A; Silva, Ana Paula.
Afiliación
  • Ventura F; Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University o
  • Muga M; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Portugal; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.
  • Coelho-Santos V; Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University o
  • Fontes-Ribeiro CA; Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University o
  • Leitão RA; Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University o
  • Silva AP; Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University o
Toxicol Lett ; 334: 53-59, 2020 Nov 01.
Article en En | MEDLINE | ID: mdl-32956829
Methamphetamine (METH) consumption is a health problem that leads to neurological and psychiatric disturbances. The cellular alterations behind these conditions have been extensively investigated and it is now well-established that METH causes cerebrovascular alterations being a key feature in drug-induced neuropathology. Although promising advances in understanding the blood-brain barrier (BBB) alterations induced by METH, there is still no available approach to counteract or diminish such effects. Interestingly, several studies show that neuropeptide Y (NPY) has an important protective role against METH-induced neuronal and glial toxicity, as well as behavioral deficits. Despite these beneficial effects of the NPY system, nothing is known about its role in brain endothelial cells under conditions of METH exposure. Thus, our aim was to unravel the effect of NPY and its receptors against METH-induced endothelial cell dysfunction. For that, we used a human brain microvascular endothelial cell line (hCMEC/D3) and our results demonstrate that endothelial cells express both NPY Y1 (Y1R) and Y2 (Y2R) receptors, but only Y2R is upregulated after METH exposure. Moreover, this drug of abuse induced endothelial cell death and elicited the production of reactive oxygen species (ROS) by these cells, which were prevented by the activation of Y2R. Additional, cell death and oxidative stress triggered by METH were dependent on the concentration of the drug. In sum, with the present study we identified for the first time the NPY system, and particularly the Y2R subtype, as a promising target to protect against METH-induced neurovascular dysfunction.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Receptores de Neuropéptido Y / Estrés Oxidativo / Células Endoteliales / Estimulantes del Sistema Nervioso Central / Metanfetamina Límite: Humans Idioma: En Revista: Toxicol Lett Año: 2020 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Receptores de Neuropéptido Y / Estrés Oxidativo / Células Endoteliales / Estimulantes del Sistema Nervioso Central / Metanfetamina Límite: Humans Idioma: En Revista: Toxicol Lett Año: 2020 Tipo del documento: Article Pais de publicación: Países Bajos