title: Bilateral upregulation of α-synuclein expression in the mouse substantia nigra by intracranial rotenone treatment.
abstract: The pesticide rotenone has been shown to cause systemic inhibition of mitochondrial complex I activity, with consequent degeneration of dopamine neurons along the nigrostriatal pathway, as observed in Parkinson's disease (PD). Recently, intracranial infusion of rotenone was found to increase the protein levels of the Lewy body constituents, α-synuclein and small ubiquitin-related modifier-1(SUMO-1), in the lesioned hemisphere of the mouse brain. These findings are supportive of a mouse model of PD, but information about the dopamine-synthesizing enzyme, tyrosine hydroxylase (TH), an essential marker of dopaminergic status, was not reported. Clarification of this issue is important because an intracranial rotenone mouse model of Parkinson's disease has not been established. Towards this end, the present study examined the effects of intracranial rotenone treatment on TH and α-synuclein immunohistochemistry in addition to forelimb motor function. Mice were unilaterally infused with either vehicle or rotenone (2μg/site) in both the medial forebrain bundle and the substantia nigra. The forelimb asymmetry (cylinder) test indicated a significant decrease in use of the contralateral forelimb in lesioned animals as compared to the sham group. Densitometric analysis revealed a significant depletion of TH immunofluorescence within the ipsilateral striatum and substantia nigra of lesioned animals. Moreover, a significant bilateral increase in α-synuclein immunofluorescence was found in the substantia nigra of lesioned mice, as compared to control animals. These findings indicate that this intracranial rotenone mouse model will be useful for studies of neurodegenerative disorders such as PD.
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada. Electronic address: candace.carriere@gmail.com.
authors.forename: Candace H
authors.initials: CH
authors.lastname: Carriere
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada. Electronic address: rachel.nh.kang@gmail.com.
authors.forename: Na Hyea
authors.initials: NH
authors.lastname: Kang
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, Faculty of Health Sciences, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada. Electronic address: niles@mcmaster.ca.
authors.forename: Lennard P
authors.initials: LP
authors.lastname: Niles
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051379:Mice; D010300:Parkinson Disease / Q000503:physiopathology; D012402:Rotenone / Q000008:administration & dosage / Q000633:toxicity*; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology*; D015854:Up-Regulation; D051844:alpha-Synuclein / Q000096:biosynthesis*
chemical_list: D007306:Insecticides; D051844:alpha-Synuclein; D012402:Rotenone
keywords: Mouse; Rotenone; Striatum; Substantia nigra; Tyrosine hydroxylase; α-synuclein