Destruction of dopaminergic neurons in the midbrain by 6-hydroxydopamine decreases hippocampal cell proliferation in rats: reversal by fluoxetine.
Destruction of dopaminergic neurons in the midbrain by 6-hydroxydopamine decreases hippocampal cell proliferation in rats: reversal by fluoxetine.
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DOI：
10.1371/journal.pone.0009260
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发表时间：
2010-02-17
期刊：
影响因子：
3.7
通讯作者：
Mori N
中科院分区：
文献类型：
--
作者：
Suzuki K;Okada K;Wakuda T;Shinmura C;Kameno Y;Iwata K;Takahashi T;Suda S;Matsuzaki H;Iwata Y;Hashimoto K;Mori N
帕金森病（PD）患者的非运动症状（如抑郁、焦虑和认知缺陷）先于运动症状出现。虽然这些症状对药物多巴胺替代疗法没有反应，但其确切的病理机制目前尚不清楚。本研究旨在探讨单侧6-羟多巴胺（6-OHDA）损伤黑质致密部（SNc）是否会影响成年大鼠脑细胞增殖，这是一种长期多巴胺能神经毒性模型。此外，我们还研究了选择性5 -羟色胺再摄取抑制剂（SSRI）氟西汀和选择性去甲肾上腺素再摄取抑制剂马普替林对单侧6-OHDA病变亚颗粒区（SGZ）细胞增殖减少的影响。在大鼠SNc中单次注射6-OHDA导致纹状体和SNc中酪氨酸羟化酶（TH）免疫反应性几乎完全丧失，以及腹侧被盖区（VTA）中TH阳性细胞和纤维的减少。另一方面，单独注射载体未显示TH免疫反应性的明显变化。单侧6-OHDA损伤SNc显著降低6-OHDA损伤同侧SGZ的细胞增殖，但对侧SGZ或室下区（SVZ）无明显影响。此外，亚慢性（14天）给药氟西汀（5mg /kg/天），而不是马普替林显著减弱单侧6-OHDA病变导致的SGZ细胞增殖的减少。本研究提示齿状回SGZ的细胞增殖可能部分受SNc和VTA的多巴胺能控制，而亚慢性氟西汀可逆转6-OHDA对SGZ细胞增殖的抑制作用。因此，氟西汀等SSRIs可能是PD患者非运动症状和运动症状的潜在治疗药物，可能与SGZ细胞增殖减少有关。
Non-motor symptoms (e.g., depression, anxiety, and cognitive deficits) in patients with Parkinson disease (PD) precede the onset of the motor symptoms. Although these symptoms do not respond to pharmacological dopamine replacement therapy, their precise pathological mechanisms are currently unclear. The present study was undertaken to examine whether the unilateral 6-hydroxydopamine (6-OHDA) lesion to the substantia nigra pars compacta (SNc), which represents a model of long-term dopaminergic neurotoxicity, could affect cell proliferation in the adult rat brain. Furthermore, we examined the effects of the selective serotonin reuptake inhibitor (SSRI) fluoxetine and the selective noradrenaline reuptake inhibitor maprotiline on the reduction in cell proliferation in the subgranular zone (SGZ) by the unilateral 6-OHDA lesion. A single unilateral injection of 6-OHDA into the rat SNc resulted in an almost complete loss of tyrosine hydroxylase (TH) immunoreactivity in the striatum and SNc, as well as in reductions of TH-positive cells and fibers in the ventral tegmental area (VTA). On the other hand, an injection of vehicle alone showed no overt change in TH immunoreactivity. A unilateral 6-OHDA lesion to SNc significantly decreased cell proliferation in the SGZ ipsilateral to the 6-OHDA lesion, but not in the contralateral SGZ or the subventricular zone (SVZ), of rats. Furthermore, subchronic (14 days) administration of fluoxetine (5 mg/kg/day), but not maprotiline significantly attenuated the reduction in cell proliferation in the SGZ by unilateral 6-OHDA lesion. The present study suggests that cell proliferation in the SGZ of the dentate gyrus might be, in part, under dopaminergic control by SNc and VTA, and that subchronic administration of fluoxetine reversed the reduction in cell proliferation in the SGZ by 6-OHDA. Therefore, SSRIs such as fluoxetine might be potential therapeutic drugs for non-motor symptoms as well as motor symptoms in patients with PD, which might be associated with the reduction in cell proliferation in the SGZ.
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影响因子：
8.6
作者：
Gonera, EG;vantHof, M;Horstink, WIM
通讯作者：
Horstink, WIM
影响因子：
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作者：
Devos, David;Dujardin, Kathy;Defebvre, Luc
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作者：
Höglinger, GU;Rizk, P;Hirsch, EC
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Hirsch, EC