Optimising validity and translational potential in rodent models of brain disorders

doi:10-3868/j.issn.2096-0689.2016.02.005

Journal of Translational Neuroscience

2016, Vol. 1

Issue (2) : 56-62 https://doi.org/10-3868/j.issn.2096-0689.2016.02.005

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Optimising validity and translational potential in rodent models of brain disorders

Anthony J Hannan

1. Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC3010, Australia 2. Department of Anatomy and Neuroscience, University of Melbourne, Parkville, VIC 3010, Australia

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Abstract Neurological and psychiatric disorders collectively constitute the greatest burden of disease. However, 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 promise in preclinical testing and then failed during clinical trials. There are a variety of potential reasons for such failures, on both the preclinical and clinical sides of the equation. In 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 in question. 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 construct 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 data. Predictive 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.

Keywords neurological diseases, psychiatric disorders, schizophrenia, Huntington’s disease, genomics, enviromics, gene-environment interactions, enviromimetics

Issue Date: 18 December 2016

Cite this article:

Anthony J Hannan. Optimising validity and translational potential in rodent models of brain disorders[J]. Journal of Translational Neuroscience, 2016, 1(2): 56-62.

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https://academic.hep.com.cn/jtn/EN/10-3868/j.issn.2096-0689.2016.02.005
https://academic.hep.com.cn/jtn/EN/Y2016/V1/I2/56

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