 Prof. John McGrath AM MD, PhD, FRANZCP Director, Epidemiology and Developmental Neurobiology Head of QBI Schizophrenia Group Queensland Centre for Mental Health Research Director of Epidemiology and Developmental Neurobiology Prof John McGrath Laboratory Head Developmental Neurobiology Dr Darryl Eyles Head of Behavioural Neuroscience Dr Tom Burne Post-docs Dr Xiaoying Cui Laboratory Manager Pauline Ko, (QHealth) PhD Students James Kesby. PhD Project: The effects of developmental vitamin D depletion on the dopaminergic system and behaviour in the rat. (Supervisors, Darryl Eyles and Tom Burne) Louise Harvey. PhD Project: Immune function and developmental vitamin D deficiency. (Supervisors, Darryl Eyles, John McGrath and Tom Burne) Lauren Harms. PhD Project: The effect of maternal vitamin D on brain development and behaviour in the mouse. (Supervisors, Tom Burne and Darryl Eyles) Claire Foldi. PhD Project: The effect of paternal age on brain development and behaviour in the mouse. (Supervisors, Tom Burne and Darryl Eyles) Research Assistants Cameron Anderson (NHMRC) Jessica Barnes (NHMRC) Suzanne Alexander (QHealth)
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Queensland Centre for Mental Health ResearchResearch DirectionsSchizophrenia is thought to be a developmental disorder with a characteristic onset in late adolescence and early adulthood. Neurodevelopmental theories suggest that genetic and nongenetic factors that disrupt early brain development contribute the risk of developing Schizophrenia. This makes the study of developmental neurobiology important for schizophrenia research. Our research team develops animal models that are (a) informed by epidemiology, and (b) cross-links with key neurobiological correlates of schizophrenia. We focus our research on epidemiologically-informed risk factors for schizophrenia that have obvious public health implications. ProjectsEffect of low prenatal vitamin D on brain development and behaviour Based on post-mortem tissue, our group has (for the first time) mapped the distribution of the VDR and of the 1 hydroxylase (the final enzyme in the activation pathways) in the normal adult human brain. The findings provide further evidence that vitamin D may operate in a fashion similar to other neurosteroids. Curiously, we found that that the large (presumably) dopaminergic cells of the substantia nigra were amongst the most immunoreactive brain areas for the VDR – dopamine has long been implicated in the neurobiology of schizophrenia. Our group has reported the temporal profile of VDR mRNA and protein expression in the developing rat brain. We have demonstrated in hippocampal cultures that vitamin D increases neurite growth in a dose-dependent fashion and increases the production of nerve growth factor (NGF). Based on fetal and neonatal rat brain tissue, we have linked the known pro-differentiating, pro-apoptotic properties of vitamin D to altered (a) rates of mitosis and cell death and (b) altered gene expression in apoptotic and mitotic pathways. With the support of the NHMRC our group was able to develop a model to explore the impact of low vitamin D during development. There is now robust evidence from in vitro and whole animal studies showing that low vitamin D levels during early life adversely affects brain development and adult behaviour. Our rat model is based on transient prenatal hypovitaminosis D – after birth the dams and pups are returned to a normal diet (and are normocalcaemic at all times). We refer to this model as the Developmental Vitamin D (DVD) model. DVD deficiency is associated with increased lateral ventricular volume in the adult offspring, reminiscent of the ventriculomegaly associated with schizophrenia. The adult behavioural phenotype of DVD-deficient rats includes enhanced locomotion in response to acute treatment with the NMDA-glutamate receptor antagonist MK-801 and diminished social behaviour. Professor John McGrath AMShort biography
John McGrath is a graduate in medicine and psychiatry from the University of Queensland. After working as a community-based psychiatrist, he moved into full-time research in 1990, at the Queensland Centre for Mental Health Research. John was Executive Director of this respected research group from 1990 to 2003. He is presently the Director of two research streams at this centre (Epidemiology, Developmental Neurobiology). In addition to his chair with the University of Queensland, he is an adjunct Professor with the School of Biomolecular and Biomedical Sciences, Griffith University. His research aims to generate and evaluate non-genetic risk factors for schizophrenia. He has forged productive cross-disciplinary collaborations linking risk factor epidemiology with developmental neurobiology (e.g. using animal models to explore candidate exposures). For example, based on clues from the epidemiology of schizophrenia, John and his group have made important discoveries about the importance of prenatal vitamin D on brain development. In addition, he has supervised major systematic reviews of the incidence and prevalence of schizophrenia. He has won several national and international awards including the Premier's Award for Medical Research, a Queensland-Smithsonian Fellowship, and a Centenary Medal for 'distinguished contribution to mental health research'. In 2005 he was awarded the Senior Research Award from the Royal Australian and New Zealand College of Psychiatrists, and a Bellagio Residency from the Rockefeller Foundation. He is on the editorial boards of several international journals. Since 1990, John has been awarded more than 30 grants from national and international peer-reviewed, competitive funding agencies. He has published over 110 peer-reviewed papers, 13 book chapters and 3 books. He has been a consultant and external reviewer for several Australian research groups and government agencies. He has given several Plenary and Keynote addresses at national and international conferences. In 2004 he delivered the prestigious NAPE (Nordic Association for Psychiatric Epidemiology) Lecture in Uppsala. Contact details [top] Prof. John McGrathQueensland Centre for Mental Health Research Queensland Brain Institute The University of Queensland Brisbane, Qld 4072, Australia. Email john_mcgrath@qcmhr.uq.edu.au Tel: (+61-7) 33466372 Fax: (+61-7) 3346 6301 Dr Darryl Eyles, BSc. Gr Dip Clin Biochem. Ph.D.Darryl Eyles is head of the Queensland Centre for Mental Health Research Neurobiology laboratory based within QBI. Our research focuses exclusively on the neurobiology of schizophrenia. In collaboration with Prof J McGrath the group has established the biological plausibility of various epidemiological risk factors for this disease. For the past seven years the group has focused on the effects of developmental vitamin D, (DVD), deficiency on brain development. Our work has led to this candidate being now taken seriously by both the basic and more recently the clinical research communities. Recently the goup initiated research into another candidate risk factor “Advanced Paternal Age.” The group approach is to create models based on these subtle risk factors and examine brain structure at a gross, cellular and molecular level. In collaboration with Dr. Tom Burne we attempt to understand how these brain alterations can affect some basic (locomotor) and complex (learning and memory) animal behaviours. Awards include a 2002 Queensland Health Award and in 2003 a Forum for European-Australian Science and Technology Cooperation award. Dr Eyles has published more than 50 scientific articles or book chapters on these subjects. Contact details Dr Darryl Eyles Queensland Centre for Mental Health Research Queensland Brain Institute The University of Queensland Brisbane, Qld 4072, Australia. Email Eyles@uq.edu.au Tel: (+61-7) 3346 6370 Fax: (+61-7) 3346 6301 Dr Tom Burne, BRurSc. (Hons) Ph.D.Tom Burne is a behavioural neuroscientist who studies brain development and behaviour in animal models of neuropsychiatric disesases, such as schizophrenia. Since obtaining his PhD in 1997 Tom has published over 40 referred papers and book chapters and along with colleagues attracted over $900,000 in grant funding (including the NHMRC and Brain Research Foundation). After obtaining his PhD with Professor Lesley Rogers at the University of New England, Tom moved to the UK for 5 years as a post-doctoral research fellow at the Babraham Institute in Cambridge. Tom returned to Australia in 2002 and is now a Senior Scientist (a permanent position) with the Queensland Centre for Mental Health Research, where he is head of the behavioural neuroscience stream working with Professor John McGrath and Dr Darryl Eyles. Contact details Dr Tom Burne Queensland Centre for Mental Health Research Queensland Brain Institute The University of Queensland Brisbane, Qld 4072, Australia. Email t.burne@uq.edu.au Fax: (+61 7) 3346 6301 [top] CollaborationsProfessor Alan Mackay-Sim, Griffith University, Brisbane Professor Francois Feron, Université de la Méditerranée, France; Professor Preben Mortensen, Universtiy of Aarhus, Denmark Professor Axel Becker, University of Magdeburg, Germany; Associate Professor Carsten Pedersen, Aarhus University, Denmark Dr. David Hougaard, Aarhus University, Denmark Professor Ron Mervis, University of South Florida USA. Dr Tim Karl, Garvan Institute, Sydney [top] Publications (2005-2007)1. Almeras, L., Eyles, D., Benech, P., Laffite, D., Villard, C., Patatian, A., Boucraut, J., Mackay-Sim, A., McGrath, J. and Feron, F., (2007). Developmental vitamin D deficiency alters brain protein expression in the adult rat: implications for neuropsychiatric disorders. Proteomics. 7, 769-780. 2. Cui, X., McGrath, J.J. Burne, T.H.J., Mackay-Sim, A. and Eyles, D.W. (2007). Maternal vitamin D depletion alters neurogenesis in the developing rat brain. International Journal of Developmental Neuroscience, 25(4), 227-232. 3. O’Loan, J., Eyles, D.W., Kesby, J., Ko, P., McGrath, J.J. and Burne T.H.J. (2007). Vitamin D deficiency during various stages of pregnancy in the rat; its impact on development and behaviour in adult offspring. Psychoneuroendocrinology, 32(3), 227-234. 4. McGrath, J. J., Barnett, A., Eyles, D., Burne, T., Pedersen, C. B. and Mortensen, P. B., (2007). The impact of nonlinear exposure-risk relationships on seasonal time-series data: modelling Danish neonatal birth anthropometric data. BMC Med Res Methodol. 7, 45. 5. McGrath, J., Scragg, R., Chant, D., Eyles, D., Burne, T. and Obradovic, D., (2007). No Association between Serum 25-Hydroxyvitamin D(3) Level and Performance on Psychometric Tests in NHANES III. Neuroepidemiology. 29, 49-54. 6. Eyles, D., Almeras, L., Benech, P., Patatian, A., Mackay-Sim, A., McGrath, J. and Feron, F., (2007). Developmental vitamin D deficiency alters the expression of genes encoding mitochondrial, cytoskeletal and synaptic proteins in the adult rat brain. Journal of Steroid Biochemistry and Molecular Biology. 103, 538-545. 7. Kesby, J., Burne, T.H.J., McGrath, J.J. and Eyles, D.W. (2006). Developmental vitamin D deficiency is associated with MK-801-induced hyperlocomotion in the adult rat: an informative animal model of schizophrenia. Biological Psychiatry, 60(6), 591-6. 8. Eyles, D.W., Rogers, F., Buller, K., McGrath, J.J., Ko, P., French, K. and Burne, T.H.J. (2006). Developmental vitamin D (DVD) deficiency in the rat alters adult behaviour independently of HPA function. Psychoneuroendocrinology, 31(8), 958-964. 9. Burne T.H.J., Johnston A.N.B., McGrath J.J. and Mackay-Sim A. (2006). Swimming behaviour and post-swimming activity in vitamin D receptor knockout mice. Brain Research Bulletin 69(1): 78-78 10. Karl T., Burne T.H.J. and Herzog H. (2006). Effect of Y1 receptor deficiency on motor activity, exploration and anxiety. Behavioural Brain Research 167(1): 87-93 11. Burne T.H.J., O’Loan J, McGrath J.J. and Eyles D.W. (2006). Hyperlocomotion associated with transient prenatal vitamin D deficiency is ameliorated by acute restraint. Behavioural Brain Research 174(1): 119-124 12. Eyles, D.W., Smith, S., Kinobe, R., Hewison, M. and McGrath, J.J., (2005). Distribution of the Vitamin D receptor and 1α-hydroxylase in human brain. Journal of Chemical Neuroanatomy. 29, 21-30. 13. Féron, F.P., Burne, T.H.J., Brown, J., Smith, E., McGrath, J.J., Mackay-Sim, A. and Eyles, D.W. (2005). Developmental vitamin D deficiency alters the adult brain. Brain Research Bulletin, 65, 141-148. 14. Ko P., Eyles D.W., Burne T., Mackay-Sim A., McGrath J. (2005) Season of birth and risk of brain tumors in adults. Neurology (Letter) 64 (7): 1317 15. McGrath J.J., Burne T., Eyles D.W. (2005) Seasonal variation in birth weight. Canadian Medical Association Journal (Letter) 173 (7): 733 16. Burne, T.H.J., McGrath, J.J., Eyles, D.W. and Mackay-Sim, A. (2005). Behavioural characterization of vitamin D receptor knockout mice. Behavioural Brain Research, 157(2), 299-308. [top] Open PositionsNHMRC funded Research Assistant[top] Useful Linkshttp://www.qcmhr.uq.edu.au/devneuro.htmhttp://www.abc.net.au/catalyst/stories/s1872656.htm http://www.biotechnews.com.au/index.php/id;1875983255 |
