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Optimising validity and translational potential in rodent models of brain disorders

Journal of Translational Neuroscience 2016年第2期1卷 56-62页

作者： Anthony J Hannan Florey Institute of Neuroscience and Mental Health Melbourne Brain CentreUniversity of MelbourneParkvilleVIC3010Australia Department of Anatomy and Neuroscience University of MelbourneParkvilleVIC3010Australia

Abstract Neurological and psychiatric disorders collectively constitute the greatest burden of ***, the human brain is the most complex of biological systems and therefore accurately modeling brain disorders presents enormous challenges. A large range of therapeutic approaches across a diverse collection of brain disorders have been found to show great promisein preclinical testing and then failed during clinical *** are a variety of potential reasons for such failures,on both the preclinical and clinical sides of the *** this article, I will focus on the key issues of validity in animal models. I will discuss two forms of construct validity, ‘genetic construct validity’ and ‘environmental construct validity’, which model specific aspects of the genome and ‘envirome’ relevant to the disorder inquestion. The generation of new gene-edited animal models has been facilitated by new technologies, the most notable of which are CRISPR-Cas systems. These and other technologies can be used to enhance contruct validity. Finally, I will discuss how face validity can be optimized, via more sophisticated cognitive, affective and motor behavioural tests,translational tools and the integration of molecular, cellular and systems *** validity cannot yet be assessed for the many preclinical models where we currently lack effective clinical interventions, however this will change as the translational pipeline is honed to deliver therapies for a range of devastating disorders.

关键词： neurological diseases psychiatric disorders schizophrenia Huntington’s disease genomics enviromics gene-environment interactions enviromimetics

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