Lack of dopaminergic inputs elongates the primary cilia of striatal neurons.
Lack of dopaminergic inputs elongates the primary cilia of striatal neurons.
复制标题
DOI：
10.1371/journal.pone.0097918
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Asanuma M
中科院分区：
文献类型：
--
作者：
Miyoshi K;Kasahara K;Murakami S;Takeshima M;Kumamoto N;Sato A;Miyazaki I;Matsuzaki S;Sasaoka T;Katayama T;Asanuma M
在啮齿类动物的大脑中，某些G蛋白偶联受体和腺苷酸环化酶3型被定位到神经元初级纤毛，一个原始的感觉细胞器突出，几乎所有的神经元。最近的一项化学筛选研究表明，许多化合物靶向多巴胺受体调节莱茵衣藻鞭毛的组装，其结构类似于脊椎动物的纤毛。在这里，我们研究了多巴胺能输入损失对啮齿动物纹状体神经元初级纤毛结构的影响，纹状体是一个接受来自中脑的主要多巴胺能投射的脑区。我们首先分析了单侧黑质纹状体多巴胺通路受损的偏侧帕金森病大鼠背外侧纹状体神经元纤毛的长度。在这些大鼠中，损伤侧的纹状体神经元纤毛明显长于非损伤侧。在小鼠中，反复注射利血平（一种多巴胺消耗剂），延长了纹状体中的神经元纤毛。多巴胺受体2型（D2）的激动剂与利血平的联合给药衰减纹状体神经元纤毛的伸长。用D2的拮抗剂重复治疗，但不是多巴胺受体1型（D1），延长纹状体神经元纤毛。此外，与野生型对照组相比，D2-null小鼠纹状体中的神经元纤毛更长。利血平治疗延长纹状体神经元纤毛在D1-null小鼠，但不是在D2-null小鼠。重复治疗与D2激动剂抑制的延长纹状体神经元纤毛的损伤侧的偏侧帕金森病大鼠。这些结果表明，缺乏多巴胺能输入后纹状体神经元纤毛的伸长归因于缺乏通过D2受体的多巴胺能传递。我们的研究结果提供了第一个证据表明，神经元纤毛的长度可以修改缺乏神经递质的输入。
In the rodent brain, certain G protein-coupled receptors and adenylyl cyclase type 3 are known to localize to the neuronal primary cilium, a primitive sensory organelle protruding singly from almost all neurons. A recent chemical screening study demonstrated that many compounds targeting dopamine receptors regulate the assembly of Chlamydomonas reinhardtii flagella, structures which are analogous to vertebrate cilia. Here we investigated the effects of dopaminergic inputs loss on the architecture of neuronal primary cilia in the rodent striatum, a brain region that receives major dopaminergic projections from the midbrain. We first analyzed the lengths of neuronal cilia in the dorsolateral striatum of hemi-parkinsonian rats with unilateral lesions of the nigrostriatal dopamine pathway. In these rats, the striatal neuronal cilia were significantly longer on the lesioned side than on the non-lesioned side. In mice, the repeated injection of reserpine, a dopamine-depleting agent, elongated neuronal cilia in the striatum. The combined administration of agonists for dopamine receptor type 2 (D2) with reserpine attenuated the elongation of striatal neuronal cilia. Repeated treatment with an antagonist of D2, but not of dopamine receptor type 1 (D1), elongated the striatal neuronal cilia. In addition, D2-null mice displayed longer neuronal cilia in the striatum compared to wild-type controls. Reserpine treatment elongated the striatal neuronal cilia in D1-null mice but not in D2-null mice. Repeated treatment with a D2 agonist suppressed the elongation of striatal neuronal cilia on the lesioned side of hemi-parkinsonian rats. These results suggest that the elongation of striatal neuronal cilia following the lack of dopaminergic inputs is attributable to the absence of dopaminergic transmission via D2 receptors. Our results provide the first evidence that the length of neuronal cilia can be modified by the lack of a neurotransmitter's input.
登录
查看更多内容
鞭毛内运输平衡外部双联微管的连续周转：对鞭毛长度控制的影响。
影响因子：
7.8
作者：
Marshall, W F;Rosenbaum, J L
通讯作者：
Rosenbaum, J L
影响因子：
6.1
作者：
Lee JH;Gleeson JG
通讯作者：
Gleeson JG
影响因子：
3.3
作者：
Händel, M;Schulz, S;Höllt, V
通讯作者：
Höllt, V
影响因子：
64.5
作者：
Gerdes JM;Davis EE;Katsanis N
通讯作者：
Katsanis N
影响因子：
64.8
作者：
通讯作者：
--