Neuregulin-1 at synapses on phrenic motoneurons.

Neuregulin-1 at synapses on phrenic motoneurons.
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DOI:
10.1002/cne.22449
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发表时间:
2010-10-15
影响因子:
2.5
通讯作者:
Mantilla, Carlos B.
Mantilla, Carlos B.
中科院分区:
医学3区
文献类型:
--
作者:
Issa, Amine N.;Zhan, Wen-Zhi;Sieck, Gary C.;Mantilla, Carlos B.

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神经调节蛋白(NRG)家族的营养因子存在于中枢和外周神经系统中,并参与许多不同细胞类型(包括运动神经元)的存活、增殖和分化。NRG 1首先以其在神经肌肉接头的形成中的作用为特征,最近显示其在调节成年大鼠中枢神经系统中的多巴胺能和胆碱能传递中起关键作用。然而,很少有人知道NRG 1在成人运动系统中的作用。运动神经元接受密集的多巴胺能和胆碱能输入。我们假设NRG 1存在于膈运动神经元的突触上。共聚焦显微镜和3D重建技术被用来确定NRG 1的分布及其与这些不同的神经递质系统的共定位。我们发现,NRG 1斑点存在于逆行标记的运动神经元周围,主要分布在运动神经元胞体和初级树突。NRG 1仅存在于突触部位(使用突触前标记物突触素鉴定),占膈运动神经元所有突触的约30%。总体而言,NRG 1免疫反应性主要存在于胆碱能突触处(75 ± 14%与囊泡乙酰胆碱转运蛋白VAChT共定位)。几乎所有(99 ± 1%)VAChT阳性突触表达NRG 1。NRG 1也存在于表达囊泡谷氨酸转运蛋白(VGLUT)2型(~6%)的突触能突触亚群中,而不存在于表达VGLUT 1型的突触中。总体而言,26 ± 6%的NRG 1突触是VGLUT 2免疫反应性的。这些发现提供了第一个证据表明,NRG 1可能调节成年运动系统的突触活动。
The neuregulin (NRG) family of trophic factors is present in the central and peripheral nervous systems and participates in the survival, proliferation and differentiation of many different cell types including motoneurons. NRG1 was first characterized by its role in the formation of the neuromuscular junction, and recently it was shown to play a crucial role in modulating glutamatergic and cholinergic transmission in the central nervous system of adult rats. However, little is known about NRG1's role in adult motor systems. Motoneurons receive dense glutamatergic and cholinergic input. We hypothesized that NRG1 is present at synapses on phrenic motoneurons. Confocal microscopy and 3D reconstruction techniques were used to determine the distribution of NRG1 and its co-localization with these different neurotransmitter systems. We found that NRG1 puncta are present around retrogradely-labeled motoneurons, and are distributed predominantly at motoneuron somata and primary dendrites. NRG1 is exclusively present at synaptic sites (identified using the presynaptic marker synaptophysin), comprising ~30% of all synapses at phrenic motoneurons. Overall, NRG1-immunoreactivity is found predominantly at cholinergic synapses (75 ± 14% co-localize with the vesicular acetylcholine transporter VAChT). Nearly all (99 ± 1%) VAChT-immunoreactive synapses expressed NRG1. NRG1 also is present at a subset of glutamatergic synapses expressing the vesicular glutamate transporter (VGLUT) type 2 (~6%) and not those expressing VGLUT type 1. Overall, 26 ± 6% of NRG1 synapses are VGLUT2 immunoreactive. These findings provide the first evidence suggesting that NRG1 may modulate synaptic activity in adult motor systems.
ARIA集中在发育中的雏鸡神经肌肉连接的突触基底层中。
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