Impaired cognitive and motor function are coincident with L-DOPA-induced dyskinesia in a model of Parkinson's disease.
Impaired cognitive and motor function are coincident with L-DOPA-induced dyskinesia in a model of Parkinson's disease.
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DOI：
10.1038/s41598-023-44869-y
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发表时间：
2023-10-17
影响因子：
4.6
通讯作者：
Lane, Emma L.
中科院分区：
文献类型：
--
作者：
Lelos, Mariah J.;Murphy, Ellen M.;Lindgren, Hanna S.;Dunnett, Stephen B.;Lane, Emma L.
多巴胺传递与运动和认知功能有关。在帕金森病 (PD) 中，使用前体药物左旋多巴 (l-DOPA) 替代多巴胺是主要的治疗方法，但长期接触会导致运动障碍 (LID) 的发作。慢性左旋多巴暴露与基因表达的变化和皮质纹状体可塑性的改变有关。本研究的目的是使用帕金森病啮齿动物模型评估长期暴露于左旋多巴对认知和运动功能的功能影响。通过两项独立实验，我们评估了在没有药物的情况下，慢性暴露于左旋多巴（l-DOPA）或对照 D2R 激动剂对完整大鼠和半侧帕金森病大鼠的运动和认知功能的影响。测量了与 LID 相关的异常不自主运动，随后收获脑组织进行免疫组织化学分析。当动物在没有药物的情况下进行测试时，长期接触左旋多巴（而不是 D2R 激动剂）会损害运动和认知功能。对这两个实验的荟萃分析允许将 l-DOPA 治疗的大鼠进一步分为发生 LID（运动障碍）的大鼠和未发生 LID（非运动障碍）的大鼠。该分析显示，认知和运动能力受损仅在运动障碍大鼠中明显，而在非运动障碍大鼠中则不然。这些数据揭示了与 LID 发作相关的可塑性改变的功能后果，并且对于了解临床症状进展具有重要意义。
Dopamine transmission has been implicated in motor and cognitive function. In Parkinson’s disease (PD), dopamine replacement using the precursor drug l-DOPA is the predominant treatment approach, but long-term exposure leads to the onset of dyskinesias (LIDs). Chronic l-DOPA exposure has been associated with changes in gene expression and altered cortico-striatal plasticity. The aim of this research was to assess the functional consequence of long-term l-DOPA exposure on cognitive and motor function using a rodent model of PD. Across two independent experiments, we assessed the impact of chronic l-DOPA exposure, or a control D2R agonist, on motor and cognitive function in intact and in hemi parkinsonian rats, in the absence of drug. Abnormal involuntary movements associated with LID were measured and brain tissues were subsequently harvested for immunohistochemical analysis. Exposure to chronic l-DOPA, but not the D2R agonist, impaired motor and cognitive function, when animals were tested in the absence of drug. A meta-analysis of the two experiments allowed further dissociation of l-DOPA -treated rats into those that developed LIDs (dyskinetic) and those that did not develop LIDs (non-dyskinetic). This analysis revealed impaired cognitive and motor performance were evident only in dyskinetic, but not in non-dyskinetic, rats. These data reveal a functional consequence of the altered plasticity associated with LID onset and have implications for understanding symptom progression in the clinic.
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影响因子：
6.1
作者：
Breger, Ludivine S.;Dunnett, Stephen B.;Lane, Emma L.
通讯作者：
Lane, Emma L.
影响因子：
64.8
作者：
CARLI, M;EVENDEN, JL;ROBBINS, TW
通讯作者：
ROBBINS, TW
影响因子：
3.4
作者：
Lelos, M. J.;Harrison, D. J.;Dunnett, S. B.
通讯作者：
Dunnett, S. B.
影响因子：
--
作者：
Cenci, M. Angela;Konradi, Christine
通讯作者：
Konradi, Christine
影响因子：
5.3
作者：
Lindgren, Hanna S.;Demirbugen, Merve;Dunnett, Stephen B.
通讯作者：
Dunnett, Stephen B.