title: Trophic factors differentiate dopamine neurons vulnerable to Parkinson's disease.
abstract: Recent studies suggest a variety of factors characterize substantia nigra neurons vulnerable to Parkinson's disease, including the transcription factors pituitary homeobox 3 (Pitx3) and orthodenticle homeobox 2 (Otx2) and the trophic factor receptor deleted in colorectal cancer (DCC), but there is limited information on their expression and localization in adult humans. Pitx3, Otx2, and DCC were immunohistochemically localized in the upper brainstem of adult humans and mice and protein expression assessed using relative intensity measures and online microarray data. Pitx3 was present and highly expressed in most dopamine neurons. Surprisingly, in our elderly subjects no Otx2 immunoreactivity was detected in dopamine neurons, although Otx2 gene expression was found in younger cases. Enhanced DCC gene expression occurred in the substantia nigra, and higher amounts of DCC protein characterized vulnerable ventral nigral dopamine neurons. Our data show that, at the age when Parkinson's disease typically occurs, there are no significant differences in the expression of transcription factors in brainstem dopamine neurons, but those most vulnerable to Parkinson's disease rely more on the trophic factor receptor DCC than other brainstem dopamine neurons.
authors.affiliation: Neuroscience Research Australia and the School of Medical Sciences, The University of New South Wales, Randwick, Sydney, New South Wales, Australia.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Reyes
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Fu
authors.forename: Kay L
authors.initials: KL
authors.lastname: Double
authors.forename: Veronica
authors.initials: V
authors.lastname: Cottam
authors.forename: Lachlan H
authors.initials: LH
authors.lastname: Thompson
authors.forename: Deniz
authors.initials: D
authors.lastname: Kirik
authors.forename: George
authors.initials: G
authors.lastname: Paxinos
authors.forename: Charles
authors.initials: C
authors.lastname: Watson
authors.forename: Helen M
authors.initials: HM
authors.lastname: Cooper
authors.forename: Glenda M
authors.initials: GM
authors.lastname: Halliday
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000818:Animals; D000075389:DCC Receptor; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D051857:Otx Transcription Factors / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000166:cytology / Q000378:metabolism
chemical_list: D000075389:DCC Receptor; C501909:DCC protein, human; C501910:Dcc protein, mouse; D018398:Homeodomain Proteins; C497659:OTX2 protein, human; D051857:Otx Transcription Factors; C497660:Otx2 protein, mouse; D011956:Receptors, Cell Surface; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C433629:homeobox protein PITX3