Protective effect of neuropeptide Y2 receptor activation against methamphetamine-induced brain endothelial cell alterations. (1st November 2020)

• Record Type: Journal Article
• Authors: Ventura, Fabiana; Muga, Mariana; Coelho-Santos, Vanessa; Fontes-Ribeiro, Carlos A.; Leitão, Ricardo A.; Silva, Ana Paula
• Is Part Of: Toxicology letters. Volume 334(2020)
• Page Start: 53
• Page End: 59
• Publication Date: 2020-11-01
• Subjects: BBB blood-brain barrier -- bFGF basic fibroblast growth factor -- BSA bovine serum albumin -- CTR control -- FBS fetal bovine serum -- H2DCFDA 2′7′- dichlorodihydrofluoresceindiacetate -- HBMVEC human brain microvascular endothelial cells -- hCMEC/D3 human cerebral microvascular endothelial cell line -- METH methamphetamine -- mRNA messenger RNA -- NCT number ClinicalTrials.gov. identifier -- NOX NADPH oxidase -- NPY neuropeptide Y -- NPY R neuropeptide Y receptor -- PBS phosphate-buffered saline solution -- PFA paraformaldehyde -- PTSD post-traumatic stress disorder -- ROS reactive oxygen species -- RT room temperature -- S.E.M. standard error of the mean -- TUNEL TdT-mediated dUTP-X nick end labelling; Brain endothelial cells -- Cell death -- Methamphetamine -- Neuropeptide Y -- Reactive oxygen species; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2020.09.013
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Brain endothelial cells express both neuropeptide Y1 and Y2 receptors. Methamphetamine (3 mM and 4 mM) promotes cell death and ROS production. Lower methamphetamine concentration (1 mM) does not interfere with endothelial cells. Activation of neuropeptide Y2 receptor has a protective effect against methamphetamine effects. Abstract: 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.