Non-invasive detection of neurochemical changes prior to overt pathology in a mouse model of spinocerebellar ataxia type 1.
Non-invasive detection of neurochemical changes prior to overt pathology in a mouse model of spinocerebellar ataxia type 1.
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DOI：
10.1111/jnc.12435
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发表时间：
2013-12
影响因子：
4.7
通讯作者：
Öz G
中科院分区：
文献类型：
--
作者：
Emir UE;Brent Clark H;Vollmers ML;Eberly LE;Öz G
脊髓小脑性共济失调1型（SCA 1）是一种遗传性、进行性和致命性运动障碍，主要影响小脑。用于检测SCA 1早期疾病的非侵入性成像标记物将促进潜在治疗的测试和实施。我们以前已经证明了1H磁共振波谱（MRS）测量的神经化学水平的敏感性进行性神经退行性病变使用SCA 1的转基因小鼠模型。为了研究与神经变性相关的非常早期的神经化学变化，在这里，我们利用了敲入小鼠模型，Sca 1154 Q/2 Q系，其显示出比转基因模型更温和的小脑病理学。我们在6、12、24和39周龄时使用9.4T MRS测量Sca 1154 Q/2 Q小鼠和野生型同窝小鼠的小脑神经化学特征，并在每个时间点评估小鼠亚组的小脑病理学。Sca 1154 Q/2 Q小鼠即使在39周时也显示出非常轻微的小脑病理学，然而，从6周开始通过MRS将其与野生型区分开。与对照组相比，Sca 1154 Q/2 Q小鼠在所有年龄段的牛磺酸和总胆碱水平均显著降低，谷氨酰胺和总肌酸水平在12周时开始升高，表明在没有明显病理学的情况下，神经化学水平对神经变性相关变化的敏感性。
Spinocerebellar ataxia type 1 (SCA1) is a hereditary, progressive and fatal movement disorder that primarily affects the cerebellum. Non-invasive imaging markers to detect early disease in SCA1 will facilitate testing and implementation of potential therapies. We have previously demonstrated the sensitivity of neurochemical levels measured by 1H magnetic resonance spectroscopy (MRS) to progressive neurodegeneration using a transgenic mouse model of SCA1. In order to investigate very early neurochemical changes related to neurodegeneration, here we utilized a knock-in mouse model, the Sca1154Q/2Q line, which displays milder cerebellar pathology than the transgenic model. We measured cerebellar neurochemical profiles of Sca1154Q/2Q mice and wild-type littermates using 9.4T MRS at ages 6, 12, 24, and 39 weeks and assessed the cerebellar pathology of a subset of the mice at each time point. The Sca1154Q/2Q mice displayed very mild cerebellar pathology even at 39 weeks, however, were distinguished from wild types by MRS starting at 6 weeks. Taurine and total choline levels were significantly lower at all ages and glutamine and total creatine levels were higher starting at 12 weeks in Sca1154Q/2Q mice than controls, demonstrating the sensitivity of neurochemical levels to neurodegeneration related changes in the absence of overt pathology.
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影响因子：
5.3
作者：
Oez, Guelin;Vollmers, Manda L.;Nelson, Christopher D.;Shanley, Ryan;Eberly, Lynn E.;Orr, Harry T.;Clark, H. Brent
通讯作者：
Clark, H. Brent
影响因子：
2.2
作者：
Garwood, M;DelaBarre, L
通讯作者：
DelaBarre, L
影响因子：
8.6
作者：
Klockgether, Thomas;Paulson, Henry
通讯作者：
Paulson, Henry
影响因子：
2.5
作者：
PETROFF, OAC;PLEBAN, LA;SPENCER, DD
通讯作者：
SPENCER, DD
影响因子：
3.7
作者：
Cudalbu C;McLin VA;Lei H;Duarte JM;Rougemont AL;Oldani G;Terraz S;Toso C;Gruetter R
通讯作者：
Gruetter R