Chapter 45 - Disease models in neurodevelopmental disorders

Abstract

Research into the mechanisms of neurodevelopmental diseases requires the use of animal models that reproduce the pathology of interest. There is a wide range of animal models, both vertebrate and invertebrate, that have been successfully employed to model neurodevelopmental disorders. Vertebrate models are closer to the humans, so they reproduce the pathology in a more accurate and relevant way. Invertebrate models are cheaper and offer a range of experimental approaches unmatched by vertebrate models, so they are also useful to study biological and health issue affecting evolutionarily conserved pathways. We use two examples to illustrate the use of animal models in neurodevelopmental disease. In the Charcot–Marie–Tooth peripheral neuropathy, there are Drosophila models of mutations in three gene families, aminoacyl-tRNA synthetases, mitochondrial dynamics, and endolysosomal pathways. In these models, neuromuscular degeneration can be reproduced by using advanced genetic manipulation and studied by behavioral, electrophysiological, and histological techniques. Neuregulin 1 is a risk factor in schizophrenia. Using the mouse as a research model, it has been possible to dissect the roles of this protein in neuronal migration during development and in the setup of the neuronal circuitry in the cerebral cortex. Both types of functions help to understand the deficit in Neuregulin 1 in this pathology.