Journal article
Trophic factors differentiate dopamine neurons vulnerable to Parkinson's disease
S Reyes, Y Fu, KL Double, V Cottam, LH Thompson, D Kirik, G Paxinos, C Watson, HM Cooper, GM Halliday
Neurobiology of Aging | ELSEVIER SCIENCE INC | Published : 2013
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..
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Grants
Awarded by Parkinson's NSW
Funding Acknowledgements
D. K. is director of a consultancy firm and has the following consultancies-with AMT, The Netherlands (research and consultancy agreement 2009-2011), with Astra-Zeneca, Sweden (research and consultancy agreement 2012-present). Stock ownership: G. M. H. owns stock in Chochlear (2004-present) and NIB Holdings (2007-present). Honoraria: K. L. D. received travel expenses and honoraria from the National Health and Medical Research Council of Australia (Research grant panel in 2010, Research Fellowships Panel, 2011). She received travel expenses from the WFN Congress on Parkinson's disease and related disorders (2011) and from the Dementia, Ageing and Neurodegenerative Disorders Interest group meeting (2012). D. K. received honoraria from a variety of governmental, academic, professional and commercial entities over the last 3 years. G. M. H. has received travel expenses from the National Health and Medical Research Council of Australia (2010, 2011 Research Fellowships Panels, 2011 Academy), International Conference on Alzheimer's Disease (2010 organizing committee and meeting), Shanghai Movement Disorders Meeting (4/2010), NIH (4/2010 Workshop on Gaucher Disease and Parkinsonism), Elan Pharmaceuticals (4/2010 and 6/2011 San Francisco seminars and 9/2011 Tokyo Parkinson's disease conference), World Parkinson's Congress (2010), International Fronto-temporal Dementia Conference (2010), International Society for Neurochemistry (2010 Asia Pacific Conference), International Synuclein Meeting (2010), International Movement Disorders Meeting (2011 organizing committee and meeting), NeuraSyn Summer School (2011), and WFN Congress on Parkinson's disease and related disorders (2011). Patents: WIPO Patent: Paxinos, G.: WO/2000/024413 Eph4A: A method for treatment: AU200012533B2. PCT Patent: Bjorklund, T., Bjorklund, A., Kirik, D. Novel viral vector construct for neuron specific optimized continuous DOPA synthesis in vivo. International patent application No: PCT/EP2010/067155. PCT Patent: Huang, Y., Rowe, D., Halliday, G., Biomarkers for Parkinson's disease. Pub. No.: WO/2009/039586. International Application No.: PCT/AU2008/001437 Publication Date: 02.04.2009, International Filing Date: 26.09.2008.Grants and other funding not associated with the project include the following. K. L. D. is funded as a chief investigator by NHMRC project grants APP1003903 (2011-2013), APP1020981, (2012-2014) APP1024226 (2012-2014), the International Science Linkages Programme (French-Australian Science and Technology programme 2010-2012) and the Coopers Brewery Foundation (2012-2013). L. H. T. is funded as a chief investigator on NHMRC project grants # 628542 (2010-2012) and # 1022637 (2012-2014). D. K. is funded as a principle investigator by the European Union-NEUGENE Coordinated Action (2008-2012), Neurasyn initial training network (2009-2013) and MEFOPA Coordinated Action (2010-2014), by the European Research Council-Starting Grant (2010-2014), by the Swedish Research Council project grant (2009-2014) and infrastructure grant (2009-2013), and as 1 of 10 coinvestigators on a Swedish Research Council Linneaus Program, Grant (2008-2017). G. P. holds NIH subaward # 2000796565 under grant # 2R01EB003543-05 via Johns Hopkins University (2009-2013), and NIH subaward # 125430/125429 under grant # AG029412-01 via the University of Texas (2007-2012). H. M. C. is funded as a Chief Investigator by NHMRC project grants # 569638 (2009-2011), # APP1010723 (2011-2013), # APP1024201 (2012-2014) and by ARC Discovery grant # DP0879769 (2008-2012). H. M. C. also has a Smart Futures Fellowship from the Queensland State Government (2008-2012). G. M. H. is funded as a Chief Investigator by NHMRC project grants # 510148 (2008-2010), # 570850 (2009-2011), # 1008307 (2011-2013), # 1022325 (2011-2013), and # 1029538 (2012-2014), ARC Linkage Infrastructure grant # LE100100074 (2010), NHMRC strategic research funds and ARC joint ageing well, ageing productively program grant # 401162 (2007-2011), the University of New South Wales Infrastructure grants (2010 and 2011) and Goldstar award (2010), Parkinson's NSW (2011), and Michael J Fox Foundation and Shake-it-up Australia (2012).Human brain tissue was received from the Sydney Brain Bank which is supported by Neuroscience Research Australia, the University of New South Wales and the National Health and Medical Research Council of Australia. The work was supported by the National Health and Medical Research Council of Australia [401101 to KD, 568605 to GP, 508992 and 1006440 to LT, 569638 to HMC, 630434 to GMH]; the Swedish Research Council [K2009-61P-20945-03-1 to DK]; the Australian Research Council [LE100100074 to GP and GMH, TS0669860 to GP and YF]; Parkinson's NSW [scholarship to SR]; Neuroscience Research Australia [Elizabeth and Michael Gilbert scholarship to SR] and the Queensland State Government [Smart Futures Fellowship to HMC]. We wish to thank the staff of the Sydney Brain Bank for there assistance, and Heidi Cartwright for the figure work.