title: Neuroprotection by 6-(methylsulfinyl)hexyl isothiocyanate in a 6-hydroxydopamine mouse model of Parkinson׳s disease.
abstract: A number of pathogenic factors have been implicated in the progression of Parkinson׳s disease (PD), including oxidative stress, mitochondrial dysfunction, inflammation, excitotoxicity, and signals mediating apoptosis cascade. 6-(methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major component in wasabi, a very popular spice in Japan and a member of the Brassica family of vegetables. This study was designed to investigate the neuroprotective effects of 6-MSITC in a PD mouse model. Mice were treated with 6-MSITC (5mg/kg twice a week) for four weeks after the unilateral intrastriatal injection of 6-hydroxydopamine (6-OHDA). On the 28th day, 6-OHDA-injected mice showed behavioral impairments, a significant decrease in tyrosine hydroxylase (TH) and an increase in apoptosis. In addition, lesioned mice showed reduced glutathione levels and glutathione-S-transferase and glutathione reductase activities. Notably, 6-MSITC demonstrated neuroprotective effects in our experimental model strongly related to the preservation of functional nigral dopaminergic neurons, which contributed to the reduction of motor dysfunction induced by 6-OHDA. Furthermore, this study provides evidence that the beneficial effects of 6-MSITC could be attributed to the decrease of apoptotic cell death and to the activation of glutathione-dependent antioxidant systems. These findings may render 6-MSITC as a promising molecule for further pharmacological studies on the investigation for disease-modifying treatment in PD.
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, via Irnerio 48, 40126 Bologna, Italy. Electronic address: fabiana.morroni@unibo.it.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Morroni
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Sita
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum - University of Bologna, Corso d׳Augusto, 237, 47900 Rimini, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tarozzi
authors.affiliation: Department for Life Quality Studies, Alma Mater Studiorum - University of Bologna, Corso d׳Augusto, 237, 47900 Rimini, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cantelli-Forti
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, via Irnerio 48, 40126 Bologna, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Hrelia
mesh_terms: D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D017879:Isothiocyanates / Q000032:analysis / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine; D010300:Parkinson Disease / Q000378:metabolism* / Q000517:prevention & control; D045442:Rotarod Performance Test; D012399:Rotation; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D017879:Isothiocyanates; D018696:Neuroprotective Agents; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D001058:Apomorphine
keywords: 6-(methylsulfinyl)hexyl isothiocyanate; 6-hydroxydopamine; Neuroprotection; Oxidative stress; Parkinson׳s disease