Cummings Damian M, Milnerwood Austen J, Dallérac Glenn M, Vatsavayai Sarat C, Hirst Mark C, Murphy Kerry P S J
Huntington's Disease Research Forum, Department of Biological Sciences, The Open University, Walton Hall, Milton Keynes, UK.
Brain Res Bull. 2007 Apr 30;72(2-3):103-7. doi: 10.1016/j.brainresbull.2006.10.016. Epub 2006 Nov 16.
Huntington's disease is a fatal neurodegenerative disorder characterised by a progressive motor, psychiatric and cognitive decline and associated with a marked loss of neurons in the cortex and striatum of affected individuals. The disease is inherited in an autosomal dominant fashion and is caused by a trinucleotide (CAG) repeat expansion in the gene encoding the protein huntingtin. Predictive genetic testing has revealed early cognitive deficits in asymptomatic gene carriers such as altered working memory, executive function and recognition memory. The perirhinal cortex is believed to process aspects of recognition memory. Evidence from primate studies suggests that decrements in neuronal firing within this cortical region encode recognition memory and that the underlying mechanism is an activity-dependent long-term depression (LTD) of excitatory neurotransmission, the converse of long-term potentiation (LTP). We have used the R6/1 mouse model of HD to assess synaptic plasticity in the perirhinal cortex. This mouse model provides an ideal tool for investigating early and progressive changes in synaptic function in HD. We report here that LTD at perirhinal synapses is markedly reduced in R6/1 mice. We also provide evidence to suggest that a reduction in dopamine D2 receptor signalling may be implicated.
亨廷顿舞蹈症是一种致命的神经退行性疾病，其特征为运动、精神和认知功能进行性衰退，并伴有患病个体大脑皮层和纹状体中神经元的显著缺失。该疾病以常染色体显性方式遗传，由编码亨廷顿蛋白的基因中三核苷酸（CAG）重复序列扩增所致。预测性基因检测已揭示无症状基因携带者存在早期认知缺陷，如工作记忆、执行功能和识别记忆的改变。鼻周皮质被认为参与处理识别记忆的各个方面。灵长类动物研究的证据表明，该皮质区域内神经元放电的减少编码了识别记忆，其潜在机制是兴奋性神经传递的活动依赖性长时程抑制（LTD），这与长时程增强（LTP）相反。我们使用亨廷顿舞蹈症的R6/1小鼠模型来评估鼻周皮质中的突触可塑性。该小鼠模型为研究亨廷顿舞蹈症突触功能的早期和进行性变化提供了理想工具。我们在此报告，R6/1小鼠鼻周突触处的LTD显著降低。我们还提供证据表明，多巴胺D2受体信号传导的减少可能与之有关。
