Improving the Utility and Translation of Animal Models for Nervous System Disorders Workshop Summary (2013) / Chapter Skim
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4 Perspectives on Standardization
4 Perspectives on Standardization
Pages 33-44
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From page 33... ...
Andrew Holmes described some of the controversy surrounding standardization of behavioral models and shared examples of interlaboratory standardization studies that have led to differing results. Timothy Bussey described the development of automated testing methods that would reduce interference introduced by experimenters in both animal and human studies.
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From page 34... ...
1 CHALLENGES TO STANDARDIZATION OF BEHAVIORAL MODELS Andrew Holmes, chief of the Laboratory of Behavioral and Genomic Neuroscience at the National Institute on Alcohol Abuse and Alcoholism, discussed standardization of behavioral models in the context of preclinical models and assays of anxiety. Holmes described several tests that have been the basis for much of the preclinical research in anxiety 1 See www.ninds.nih.gov/funding/transparency_in_reporting_guidance.pdf.
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From page 35... ...
Using these inbred strains restricts the amount of variability in the population and presumably increases the ability to detect influences due to an environmental or a procedural difference. The first study Holmes described compared the results of standard tests and assays for anxiety across four different laboratories involved in a consortium project (Mandillo et al., 2008)
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From page 36... ...
They also noted the challenges of behavioral research standardization because there are many differing opinions on the "best" way to assay behavior. As a result, they went on to say that "it is not clear whether standardization of behavioral assays would markedly improve future replication of results across laboratories" (Crabbe et al., 1999 p.
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From page 37... ...
Even if standardization will improve the reproducibility of behavioral tests, Holmes concluded, we also need to develop novel endpoints that might be less liable to these issues. DEVELOPING TRANSLATABLE COGNITIVE ASSAYS Timothy Bussey, professor in the department of experimental psychology at the University of Cambridge, focused his comments on behavioral cognitive assessment in animal models.
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From page 38... ...
A specialized apparatus incorporates a computer monitor, touchscreen and food magazine that dispenses a pellet when the animal responds to the challenge correctly. In another example, Bussey described a test of spatial and nonspatial learning and memory, visual reversal learning, and attention using the triple transgenic Alzheimer's disease (3xTgAD)
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From page 39... ...
Models of Alzheimer's disease, including transgenic mouse models, have been very informative in dissecting this complexity, Mucke said. Much Alzheimer's research has focused on the structural alterations found in the human disease (e.g., amyloid plaque formation)
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. One example of extrapolation of therapeutic findings from a mouse model to the human condition was the finding that immunization against amyloid beta clears amyloid plaques (Nicoll al., 2006; Schenk et al., 1999)
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From page 41... ...
If a transgenic mouse model simulates only one of the causes, a treatment effect may be observed, but in the larger context of the human disease, there may only be partial benefit. Mucke referred workshop participants to a recent review on best practices for preclinical animal studies in Alzheimer's disease (Shineman et al., 2011)
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From page 42... ...
Koroshetz noted that for spinal cord injury studies, when NINDS was not able to obtain the same results as the original investigators, they brought those investigators into the NINDS laboratories to help reproduce the results. Mucke expressed concern that, while an academic researcher is usually committed to studying one area, such as behavior, for the length of
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A participant with a pharmaceutical background countered that pharmaceutical researchers are equally dedicated scientists who work hard to maintain their expertise. A participant pointed out that this workshop is focused on translation and exploring avenues to reduce clinical trial failures.
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From page 44... ...
Complex genetic strains have been derived from crossing a dozen or so different inbred strains, producing a population that is genetically as complex as a human population, Holmes said. These strains have a place in research for answering specific questions, such as the genetic basis of a particular phenotype.
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