Cognitive Deficits in Huntington’s Disease: Insights from Animal Models

被引：0
作者：
Elizabeth A. Wang
Carlos Cepeda
Michael S. Levine
机构：
[1] David Geffen School of Medicine,Intellectual and Developmental Disabilities Research Center, Semel Institute for Neuroscience and Human Behavior
[2] University of California Los Angeles,undefined
来源：
Current Translational Geriatrics and Experimental Gerontology Reports | 2012年 / 1卷 / 1期
关键词：
Animals models; Huntington’s disease; Synaptic plasticity; Cognition; Long-term potentiation; Long-term depression; N-methyl-D-aspartate receptor; Dopamine; Metabolic mapping; Hippocampus; Cerebral cortex; Thalamus; Striatum; Aging;
D O I：
10.1007/s13670-011-0005-y
中图分类号：
学科分类号：
摘要：
Although Huntington’s disease (HD) is commonly recognized as a movement disorder, cognitive dysfunction is an intrinsic feature of the disease that often manifests before the onset of chorea. Neuronal loss has been demonstrated in anatomical regions known to be substrates of learning and memory, but cell loss is presaged by functional alterations. Changes in long-term synaptic plasticity, a substrate of memory processes, emerge in cognitive domains such as the hippocampus, the cortex, and the striatum. Insights from animal models provide mechanistic explanations of how long-term synaptic plasticity is altered in these regions. Glutamate and dopamine receptors play a crucial role in such changes and progress in this area of investigation has made significant strides in recent years. Based on these discoveries, novel therapies are being developed to improve clinical outcomes and ameliorate cognitive symptoms of HD.
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页码：29 / 38
页数：9
相关论文
共 369 条
[51]  
Degenetais E(2003)Transgenic rat model of Huntington’s disease Hum Mol Genet 12 617-47
[52]  
Glowinski J(2006)Selective striatal neuron loss and alterations in behavior correlate with impaired striatal function in Huntington’s disease transgenic rats Neurobiol Dis 22 538-92
[53]  
Grahn JA(1999)A YAC mouse model for Huntington’s disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration Neuron 23 181-67
[54]  
Parkinson JA(2003)Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease Hum Mol Genet 12 1555-35
[55]  
Owen AM(2005)Selective degeneration and nuclear localization of mutant huntingtin in the YAC128 mouse model of Huntington disease Hum Mol Genet 14 3823-5
[56]  
Packard MG(2009)In vivo evidence for NMDA receptor-mediated excitotoxicity in a murine genetic model of Huntington disease J Neurosci 29 3200-32
[57]  
Knowlton BJ(1999)Enhanced sensitivity to N-methyl-D-aspartate receptor activation in transgenic and knockin mouse models of Huntington’s disease J Neurosci Res 58 515-44
[58]  
Haber S(2001)Neurological abnormalities in a knock-in mouse model of Huntington’s disease Hum Mol Genet 10 137-74
[59]  
McFarland NR(1999)A Huntington’s disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice Hum Mol Genet 8 763-13
[60]  
Kimura M(2000)Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice Hum Mol Genet 9 503-76
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