Characterization of oromotor and limb motor dysfunction in the DJ1 -/- model of Parkinson disease.
Characterization of oromotor and limb motor dysfunction in the DJ1 -/- model of Parkinson disease.
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DOI：
10.1016/j.bbr.2017.10.036
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发表时间：
2018-02-26
影响因子：
2.7
通讯作者：
Ciucci MR
中科院分区：
文献类型：
--
作者：
Yang KM;Blue KV;Mulholland HM;Kurup MP;Kelm-Nelson CA;Ciucci MR
帕金森病(PD)是一种严重损害感觉运动功能的疾病，包括颅/口运动和肢体运动障碍。然而，帕金森病相关功能障碍的发病、进展和神经相关性还知之甚少。为了解决这一差距，我们使用了帕金森病的遗传大鼠模型DJ1−/−，并假设运动缺陷会在疾病过程的早期表现出来，本质上是进行性的，并与脑干结构中与感觉运动功能相关的病理有关。本研究比较了纯合子DJ1−/−雄性大鼠和年龄匹配的野生型对照大鼠。在2、4、6、8个月龄时，对其进行性头颅感觉运动功能(超声发声和舌运动功能)和肢体运动功能(锥形平衡木)进行分析。此外，还对蓝斑进行了酪氨酸羟化酶细胞计数，并与行为测量结果相关联。我们发现，与野生型对照相比，DJ1−/−显示出超声波发声缺陷以及进行性的口述运动(舌头)缺陷。随着时间的推移，DJ1−/−大鼠跨过一根锥形平衡木，其穿越速度显著降低。此外，在DJ1型−/−中，蓝斑内酪氨酸羟化酶阳性细胞显著减少，且与运动行为呈负相关。描述DJ1PD的−/−模型为定义与人类早期PD病理平行的行为和早发生物标志物提供了重要的基础性工作。
Parkinson disease (PD) is devastating to sensorimotor function that includes cranial/oromotor and limb motor deficits. However, the onset, progression, and neural correlates of PD-related dysfunctions are poorly understood. To address this gap, we used a genetic rat model of PD, DJ1 −/−, and hypothesized that motor deficits would manifest early in the disease process, be progressive in nature, and be related to pathologies in brainstem structures associated with sensorimotor function. The present study compares homozygous DJ1 −/− male rats to age-matched wild type controls. Progressive cranial sensorimotor function (ultrasonic vocalizations and tongue motor performance) and limb motor function (tapered balance beam) was analyzed at 2, 4, 6, and 8 months of age. Additionally, tyrosine hydroxylase cell counts were performed in the locus coeruleus and correlated to behavioral measures. We found that compared to wild type controls, DJ1 −/− show deficits in ultrasonic vocalizations as well as oromotor (tongue) deficits that were progressive. Overtime, DJ1 −/− rats cross a tapered balance beam with significantly decreased speed of traversal. Additionally, in the DJ1 −/−, tyrosine hydroxylase positive cells in the locus coeruleus are significantly reduced and are negatively correlated to oromotor behaviors. Characterizing the DJ1 −/− model of PD provides important foundational work necessary to define behavioral and early-onset biomarkers that parallels early-stage PD pathology in humans.
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影响因子：
56.9
作者：
Bonifati, V;Rizzu, P;Heutink, P
通讯作者：
Heutink, P
影响因子：
2
作者：
Basken, Jaime N.;Connor, Nadine P.;Ciucci, Michelle R.
通讯作者：
Ciucci, Michelle R.
影响因子：
1.9
作者：
Fuh, JL;Lee, RC;Liu, HC
通讯作者：
Liu, HC
影响因子：
5.3
作者：
Johnson AM;Grant LM;Schallert T;Ciucci MR
通讯作者：
Ciucci MR
影响因子：
2.5
作者：
ALDES, LD
通讯作者：
ALDES, LD