Genetic mouse models of Huntington's and Parkinson's diseases: illuminating but imperfect.

Mental Retardation Research Center, The David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Trends in Neurosciences (Impact Factor: 12.9). 12/2004; 27(11):691-7. DOI: 10.1016/j.tins.2004.08.008
Source: PubMed

ABSTRACT Genetic mouse models based on identification of genes that cause Huntington's and Parkinson's diseases have revolutionized understanding of the mechanistic pathophysiological progression of these disorders. These models allow the earliest manifestations of the diseases to be identified, and they display behavioral, neuropathological and electrophysiological deficits that can be followed over time in mechanistic and drug studies. An intriguing feature is that they do not reproduce the relatively selective and massive cell loss characterizing the human diseases. There is more information on Huntington's disease models because the disorder involves a single gene that was identified over ten years ago; genetic mutations causing Parkinson's disease are rare and were discovered more recently, and models of the disease have been generated only within the past few years.

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    ABSTRACT: Huntington's disease (HD) is a progressive neurodegenerative disorder that profoundly impairs corticostriatal information processing. While late stage pathology includes cell death, the appearance of motor symptoms parallels more subtle changes in neuronal function and synaptic integration. Because of the difficulty in modeling the disease and the complexity of the corticostriatal network, understanding the mechanisms driving pathology has been slow to develop. In recent years, advances in animal models and network analysis tools have begun to shed light on the circuit-specific deficits. These studies have revealed a progressive impairment of corticostriatal synaptic signaling in subpopulations of striatal neurons, turning classical excitotoxicity models of HD upside down. Disrupted brain derived neurotrophic factor signaling appears to be a key factor in this decline. Copyright © 2015 Elsevier Ltd. All rights reserved.
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