Titolo:  Metformin prevented dopaminergic neurotoxicity induced by 3,4-Methylenedioxymethamphetamine administration
Data di pubblicazione:  2016
Data di prima pubblicazione on-line:  2016
Autori:  Porceddu, PF; Ishola, IO; Contu, L; Morelli, M
Numero degli autori:  4
Lingua:  Inglese
Presenza coautori internazionali: 
Volume:  30
Fascicolo:  1
Pagina iniziale:  101
Pagina finale:  109
Numero di pagine:  9
Digital Object Identifier (DOI):  http://dx.doi.org/10.1007/s12640-016-9633-5
Codice identificativo Pubmed:  27251371
Codice identificativo Scopus:  2-s2.0-84973121878
Codice identificativo ISI:  WOS:000379058100009
Parole Chiave:  Caudate putamen, MDMA, Neurodegeneration, Neuroprotection, Substantia nigra, Tyrosine hydroxylase, Neuroscience (all), Medicine (all), Toxicology
Abstract:  Metformin, a well-known antidiabetic drug, has recently been proposed to promote neurogenesis and to have a neuroprotective effect on the neurodegenerative processes induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in models of Parkinson’s disease. Interestingly, metformin has antioxidant properties and is involved in regulating the production of cytokines released during the neuroinflammatory process. Several studies have reported that 3,4-methylenedioxymethamphetamine (MDMA), a recreational drug mostly consumed by young adults, produces a persistent loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) and caudate putamen (CPu) of mice. The aim of this study was to investigate the potential neuroprotective effect of metformin against short- and long-term neurotoxicity induced by MDMA and its role on MDMA-induced hyperthermia. Adult mice received metformin (2 × 200 mg/kg, 11-h intervals, administered orally), MDMA (4 × 20 mg/kg, 2-h interval, administered intraperitoneally), or MDMA plus metformin (2 × 200 mg/kg, 1 h before the first MDMA administration and 4 h after the last). On the second and third day, mice were treated with vehicle or metformin (1 × 200 mg/kg) and sacrificed 48 h and 7 days after the last MDMA administration. The neuroprotective effect of metformin on MDMA-induced dopaminergic damage was evaluated by dopamine transporter (DAT) and tyrosine hydroxylase (TH) immunohistochemistry in SNc and CPu. Metformin prevented the MDMA-induced loss of TH-positive neurons in the SNc and TH- and DAT-positive fibers in CPu, both at 48 h and 7 days after the last MDMA administration. These results show that metformin is neuroprotective against the short- and long-lasting dopaminergic neurodegeneration induced by MDMA
Tipologia: 1.1 Articolo in rivista

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