The effects of chronic levodopa treatments on the neuronal firing properties of the subthalamic nucleus and substantia nigra reticulata in hemiparkinsonian rhesus monkeys.
The effects of chronic levodopa treatments on the neuronal firing properties of the subthalamic nucleus and substantia nigra reticulata in hemiparkinsonian rhesus monkeys.
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DOI：
10.1016/j.expneurol.2010.12.001
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发表时间：
2011-03
影响因子：
5.3
通讯作者：
Subramanian, Thyagarajan
中科院分区：
文献类型：
--
作者：
Gilmour, Timothy P.;Lieu, Christopher A.;Nolt, Mark J.;Piallat, Brigitte;Deogaonkar, Milind;Subramanian, Thyagarajan
关键词：
多巴胺替代疗法与左旋多巴（LD）是目前最有效的药物治疗帕金森病（PD），神经退行性疾病的特征是基底神经节电生理功能障碍。慢性LD治疗对帕金森病患者丘脑底核（subthalamic nucleus，简称STN）和黑质网状核（substantia nigra reticulata，简称SNR）电生理活动的影响尚不清楚。在本研究中，我们研究了慢性LD治疗对稳定的偏侧帕金森病猴模型中的纹状体和SNR神经元的放电频率和放电模式的影响。我们还评估了LD治疗前后两个核的局部场电位。在稳定的偏侧帕金森病状态下，EEG和SNR的平均放电频率分别为42.6±3.5Hz（平均值±SEM）和52.1±5.7Hz。慢性间歇性LD暴露诱导帕金森综合征明显改善，无明显药物诱导的运动并发症。LD处理对海马神经元的平均放电频率（41.3±3.3Hz）和爆发性放电模式无明显影响。然而，LD处理诱导SNR神经元的平均放电频率显著降低至36.2±3.3Hz（p<0.05），并有增加爆发性的趋势。从信噪比和信噪比的尖峰序列的熵是不变的LD处理，而有一个移动到更高的频带的频谱功率在LFPs。慢性LD治疗无法减少在脑干和SNR中的突发性放电模式，应进一步检查作为LD治疗难治性PD症状的潜在病理生理机制。
Dopamine replacement therapy with levodopa (LD) is currently the most effective pharmacological treatment for Parkinson's disease (PD), a neurodegenerative disorder characterized by dysfunction of basal ganglia electrophysiology. The effects of chronic LD treatments on the electrophysiological activity of the subthalamic nucleus (STN) and the substantia nigra reticulata (SNR) in parkinsonism are not clear. In the present study we examined the effects of chronic LD treatments on the firing rate and firing pattern of STN and SNR neurons in the stable hemiparkinsonian monkey model of PD. We also evaluated local field potentials of both nuclei before and after LD treatments. In a stable hemiparkinsonian state, STN and SNR had a mean firing rate of 42.6±3.5Hz (mean±SEM) and 52.1±5.7Hz, respectively. Chronic intermittent LD exposure induced marked amelioration of parkinsonism with no apparent drug-induced motor complications. LD treatments did not significantly change the mean firing rate of STN neurons (41.3±3.3Hz) or bursting neuronal firing patterns. However, LD treatments induced a significant reduction of the mean firing rates of SNR neurons to 36.2±3.3Hz (p<0.05) and a trend toward increased burstiness. The entropy of the spike sequences from STN and SNR was unchanged by LD treatment, while there was a shift of spectral power into higher frequency bands in the LFPs. The inability of chronic LD treatments to reduce the bursty firing patterns in the STN and SNR should be further examined as a potential pathophysiological mechanism for PD symptoms that are refractory to LD treatments.
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影响因子：
3.4
作者：
Kühn, AA;Kupsch, A;Brown, P
通讯作者：
Brown, P
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