Abstract：
BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a successful treatment option in Parkinson\'s disease (PD) for different motor and non-motor symptoms, but has been linked to postoperative cognitive impairment.
OBJECTIVE: Since both dopaminergic and norepinephrinergic neurotransmissions play important roles in symptom development, we analysed STN-DBS effects on dopamine and norepinephrine availability in different brain regions and morphological alterations of catecholaminergic neurons in the 6-hydroxydopamine PD rat model.
METHODS: We applied one week of continuous unilateral STN-DBS or sham stimulation, respectively, in groups of healthy and 6-hydroxydopamine-lesioned rats to quantify dopamine and norepinephrine contents in the striatum, olfactory bulb and dentate gyrus. In addition, we analysed dopaminergic cell counts in the substantia nigra pars compacta and area tegmentalis ventralis and norepinephrinergic neurons in the locus coeruleus after one and six weeks of STN-DBS.
RESULTS: In 6-hydroxydopamine-lesioned animals, one week of STN-DBS did not alter dopamine levels, while striatal norepinephrine levels were decreased. However, neither one nor six weeks of STN-DBS altered dopaminergic neuron numbers in the midbrain or norepinephrinergic neuron counts in the locus coeruleus. Dopaminergic fibre density in the dorsal and ventral striatum also remained unchanged after six weeks of STN-DBS. In healthy animals, one week of STN-DBS resulted in increased dopamine levels in the olfactory bulb and decreased contents in the dentate gyrus, but had no effects on norepinephrine availability.
CONCLUSIONS: STN-DBS modulates striatal norepinephrinergic neurotransmission in a PD rat model. Additional behavioural studies are required to investigate the functional impact of this finding.
OBJECTIVE: Since both dopaminergic and norepinephrinergic neurotransmissions play important roles in symptom development, we analysed STN-DBS effects on dopamine and norepinephrine availability in different brain regions and morphological alterations of catecholaminergic neurons in the 6-hydroxydopamine PD rat model.
METHODS: We applied one week of continuous unilateral STN-DBS or sham stimulation, respectively, in groups of healthy and 6-hydroxydopamine-lesioned rats to quantify dopamine and norepinephrine contents in the striatum, olfactory bulb and dentate gyrus. In addition, we analysed dopaminergic cell counts in the substantia nigra pars compacta and area tegmentalis ventralis and norepinephrinergic neurons in the locus coeruleus after one and six weeks of STN-DBS.
RESULTS: In 6-hydroxydopamine-lesioned animals, one week of STN-DBS did not alter dopamine levels, while striatal norepinephrine levels were decreased. However, neither one nor six weeks of STN-DBS altered dopaminergic neuron numbers in the midbrain or norepinephrinergic neuron counts in the locus coeruleus. Dopaminergic fibre density in the dorsal and ventral striatum also remained unchanged after six weeks of STN-DBS. In healthy animals, one week of STN-DBS resulted in increased dopamine levels in the olfactory bulb and decreased contents in the dentate gyrus, but had no effects on norepinephrine availability.
CONCLUSIONS: STN-DBS modulates striatal norepinephrinergic neurotransmission in a PD rat model. Additional behavioural studies are required to investigate the functional impact of this finding.
摘要：
背景：丘脑下核深部脑刺激（STN-DBS）是帕金森病（PD）中不同运动和非运动症状的成功治疗选择，但与术后认知障碍有关。
目的：由于多巴胺能和去甲肾上腺素能神经传递在症状发展中起重要作用，我们在6-羟基多巴胺PD大鼠模型中分析了STN-DBS对不同脑区多巴胺和去甲肾上腺素可用性的影响以及儿茶酚胺能神经元的形态学改变.
方法：我们应用了一周的连续单侧STN-DBS或假刺激，分别,在健康和6-羟基多巴胺损伤的大鼠组中，量化纹状体中多巴胺和去甲肾上腺素的含量，嗅球和齿状回。此外,在STN-DBS治疗1周和6周后,我们分析了黑质致密部和蓝斑部位被膜腹侧区和去甲肾上腺素能神经元的多巴胺能细胞计数.
结果：在6-羟基多巴胺损伤的动物中，一周的STN-DBS没有改变多巴胺水平，而纹状体去甲肾上腺素水平下降。然而,STN-DBS的一周或六周都不会改变中脑多巴胺能神经元数量或蓝斑基因座去甲肾上腺素能神经元数量。STN-DBS六周后，背侧和腹侧纹状体中的多巴胺能纤维密度也保持不变。在健康的动物中，一周的STN-DBS导致嗅球多巴胺水平升高，齿状回含量降低，但对去甲肾上腺素的供应没有影响.
结论：STN-DBS在PD大鼠模型中调节纹状体去甲肾上腺素能神经传递。需要额外的行为研究来调查这一发现的功能影响。
目的：由于多巴胺能和去甲肾上腺素能神经传递在症状发展中起重要作用，我们在6-羟基多巴胺PD大鼠模型中分析了STN-DBS对不同脑区多巴胺和去甲肾上腺素可用性的影响以及儿茶酚胺能神经元的形态学改变.
方法：我们应用了一周的连续单侧STN-DBS或假刺激，分别,在健康和6-羟基多巴胺损伤的大鼠组中，量化纹状体中多巴胺和去甲肾上腺素的含量，嗅球和齿状回。此外,在STN-DBS治疗1周和6周后,我们分析了黑质致密部和蓝斑部位被膜腹侧区和去甲肾上腺素能神经元的多巴胺能细胞计数.
结果：在6-羟基多巴胺损伤的动物中，一周的STN-DBS没有改变多巴胺水平，而纹状体去甲肾上腺素水平下降。然而,STN-DBS的一周或六周都不会改变中脑多巴胺能神经元数量或蓝斑基因座去甲肾上腺素能神经元数量。STN-DBS六周后，背侧和腹侧纹状体中的多巴胺能纤维密度也保持不变。在健康的动物中，一周的STN-DBS导致嗅球多巴胺水平升高，齿状回含量降低，但对去甲肾上腺素的供应没有影响.
结论：STN-DBS在PD大鼠模型中调节纹状体去甲肾上腺素能神经传递。需要额外的行为研究来调查这一发现的功能影响。
