Assessment of motor function, sensory motor gating and recognition memory in a novel BACHD transgenic rat model for huntington disease.
Assessment of motor function, sensory motor gating and recognition memory in a novel BACHD transgenic rat model for huntington disease.
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DOI：
10.1371/journal.pone.0068584
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ellenbroek B
中科院分区：
文献类型：
--
作者：
Abada YS;Nguyen HP;Schreiber R;Ellenbroek B
亨廷顿病（HD）通常首先通过出现运动症状来诊断;随后通过亨廷顿（HTT）基因中存在扩增的CAG重复序列（> 35）来证实诊断。最近建立了一种携带有97个CAG-CAA重复的人全长突变HTT的BACHD大鼠模型。BACHD大鼠的行为表型将有助于确定该模型的有效性及其在临床前药物发现研究中的潜在用途。本研究旨在描述BACHD大鼠运动，感觉运动和认知缺陷的逐步出现。从1至12月龄测试野生型和转基因大鼠。选择运动测试来测量自发运动活动（开放场）和步态协调。感觉运动门控进行了评估，在声学惊吓反应范式和识别记忆进行了评价，在一个对象的识别测试。转基因大鼠在1个月大时表现出活动过度，在4个月大时开始表现出活动减退。2个月时，在旋转棒试验中出现运动协调不平衡，12个月时在猫步试验中观察到步态异常。观察到微妙的感觉运动变化，而物体识别在12个月大的BACHD大鼠中未受损。目前的BACHD大鼠模型重现了HD患者的某些症状，特别是明显的运动缺陷。一个微妙的神经心理表型被发现，需要进一步的研究，以充分解决感觉运动表型和潜在的使用BACHD大鼠的药物发现的目的。
Huntington disease (HD) is frequently first diagnosed by the appearance of motor symptoms; the diagnosis is subsequently confirmed by the presence of expanded CAG repeats (> 35) in the HUNTINGTIN (HTT) gene. A BACHD rat model for HD carrying the human full length mutated HTT with 97 CAG-CAA repeats has been established recently. Behavioral phenotyping of BACHD rats will help to determine the validity of this model and its potential use in preclinical drug discovery studies. The present study seeks to characterize the progressive emergence of motor, sensorimotor and cognitive deficits in BACHD rats. Wild type and transgenic rats were tested from 1 till 12 months of age. Motor tests were selected to measure spontaneous locomotor activity (open field) and gait coordination. Sensorimotor gating was assessed in acoustic startle response paradigms and recognition memory was evaluated in an object recognition test. Transgenic rats showed hyperactivity at 1 month and hypoactivity starting at 4 months of age. Motor coordination imbalance in a Rotarod test was present at 2 months and gait abnormalities were seen in a Catwalk test at 12 months. Subtle sensorimotor changes were observed, whereas object recognition was unimpaired in BACHD rats up to 12 months of age. The current BACHD rat model recapitulates certain symptoms from HD patients, especially the marked motor deficits. A subtle neuropsychological phenotype was found and further studies are needed to fully address the sensorimotor phenotype and the potential use of BACHD rats for drug discovery purposes.
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影响因子：
4.2
作者：
HAMM, RJ;PIKE, BR;JENKINS, LW
通讯作者：
JENKINS, LW
影响因子：
16.2
作者：
Kordasiewicz HB;Stanek LM;Wancewicz EV;Mazur C;McAlonis MM;Pytel KA;Artates JW;Weiss A;Cheng SH;Shihabuddin LS;Hung G;Bennett CF;Cleveland DW
通讯作者：
Cleveland DW
DOI：
10.1016/j.bbrc.2004.08.035
发表时间：
2004-10-01
影响因子：
3.1
作者：
Bezprozvanny, I;Hayden, MR
通讯作者：
Hayden, MR
影响因子：
10.6
作者：
Castellanos, FX;Fine, EJ;Hallett, M
通讯作者：
Hallett, M
影响因子：
16.2
作者：
Crook ZR;Housman D
通讯作者：
Housman D