title: Imidazolium salt (DBZIM) reduces gliosis in mice treated with neurotoxicant 2'-CH(3) -MPTP.
abstract: We have recently identified a class of imidazolium salts (IMSs) with antioxidative property and can function as scavengers for radical oxygen species (ROS) [18]. Here, we investigate one of the IMSs, 1,3-bisbenzylimidazolium bromide (DBZIM), for its possible role in attenuating neurotoxicity and gliosis in the retina and the brain induced by a Parkinsonian neurtoxicant, methyl-4(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'-CH(3) -MPTP), which is a free radical generating agent. In this study, we employ a molecular retinal imaging method, which we recently developed in a transgenic mouse model expressing green fluorescent protein (GFP) under the control of glial fibrillary acidic protein (GFAP) promoter [14], to assess the efficacy of DBZIM, since currently no in vitro system with a sufficient complexity is available for accurately assessing a compound's efficacy. The longitudinal imaging results showed DBZIM can effectively suppress the neurotoxicant-induced retinal gliosis. Immunohistochemistry performed on the postmodern mouse brain confirmed that DBZIM also reduced striatal gliosis, and concomitantly attenuated the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). These findings suggest that DBZIM could be a useful small molecular compound for studying neurotoxicity and neuroprotection in the retina and the brain.
authors.affiliation: Institute of Bioengineering and Nanotechnology, Singapore.
authors.forename: Gideon
authors.initials: G
authors.lastname: Ho
authors.forename: Saravana
authors.initials: S
authors.lastname: Kumar
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Ke
authors.forename: Hugh Hiu Nam
authors.initials: HH
authors.lastname: Chan
authors.forename: Nur-Afidah Mohamed
authors.initials: NA
authors.lastname: Suhaimi
authors.forename: Yin Ling
authors.initials: YL
authors.lastname: Kng
authors.forename: Yugen
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lang
authors.initials: L
authors.lastname: Zhuo
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives*; D000818:Animals; D001921:Brain / Q000473:pathology; D004298:Dopamine / Q000502:physiology; D018492:Dopamine Antagonists / Q000633:toxicity*; D005123:Eye / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics; D005911:Gliosis / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D049452:Green Fluorescent Proteins; D007093:Imidazoles / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020267:MPTP Poisoning / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D017072:Neostriatum / Q000201:enzymology; D009474:Neurons / Q000473:pathology; D009887:Ophthalmoscopy; D012160:Retina / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: C560871:1,3-bisbenzylimidazolium; D018492:Dopamine Antagonists; D005904:Glial Fibrillary Acidic Protein; D007093:Imidazoles; C048977:1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine; D049452:Green Fluorescent Proteins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D013482:Superoxide Dismutase; D004298:Dopamine
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