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Articles by J. J McGrath
Total Records ( 2 ) for J. J McGrath
  N Matigian , G Abrahamsen , R Sutharsan , A. L Cook , A. M Vitale , A Nouwens , B Bellette , J An , M Anderson , A. G Beckhouse , M Bennebroek , R Cecil , A. M Chalk , J Cochrane , Y Fan , F Feron , R McCurdy , J. J McGrath , W Murrell , C Perry , J Raju , S Ravishankar , P. A Silburn , G. T Sutherland , S Mahler , G. D Mellick , S. A Wood , C. M Sue , C. A Wells and A. Mackay Sim
  Nicholas Matigian, Greger Abrahamsen, Ratneswary Sutharsan, Anthony L. Cook, Alejandra M. Vitale, Amanda Nouwens, Bernadette Bellette, Jiyuan An, Matthew Anderson, Anthony G. Beckhouse, Maikel Bennebroek, Rowena Cecil, Alistair M. Chalk, Julie Cochrane, Yongjun Fan, Francois Feron, Richard McCurdy, John J. McGrath, Wayne Murrell, Chris Perry, Jyothy Raju, Sugandha Ravishankar, Peter A. Silburn, Greg T. Sutherland, Stephen Mahler, George D. Mellick, Stephen A. Wood, Carolyn M. Sue, Christine A. Wells, and Alan Mackay-Sim There is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson’s disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson’s disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery.

  J. J McGrath and L. J. Richards
 

Schizophrenia epidemiology can provide us with valuable information to guide research directions. However, while epidemiology is useful for generating candidate risk factors, it can not always deliver studies that prove causality. We argue that the field needs more translational research that links schizophrenia epidemiology with molecular, cellular, and behavioral neuroscience. Cross-disciplinary projects related to candidate genetic or nongenetic risk factors not only can address the biological plausibility of these factors, but they can serve as catalysts for discovery in neuroscience. This type of cross disciplinary research is likely to be more efficient compared to clinically dislocated basic neuroscience. Examples of this type of translational research are provided based on (a) the impact of prenatal nutrition and prenatal infection on brain development and (b) understanding the causes and consequences of agenesis of the corpus callosum. We need to build shared discovery platforms that encourage greater cross-fertilization between schizophrenia epidemiology and basic neuroscience research.

 
 
 
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