Mice deficient for galanin receptor 2 have decreased neurite outgrowth from adult sensory neurons and impaired pain-like behaviour.
Mice deficient for galanin receptor 2 have decreased neurite outgrowth from adult sensory neurons and impaired pain-like behaviour.
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DOI：
10.1111/j.1471-4159.2006.04143.x
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发表时间：
2006-11
影响因子：
4.7
通讯作者：
Wynick D
中科院分区：
文献类型：
--
作者：
Hobson SA;Holmes FE;Kerr NC;Pope RJ;Wynick D
周围神经损伤后，神经肽甘丙肽的表达在成人背根神经节（DRG）内显著上调。我们以前已经证明，甘丙肽敲除（Gal-KO）小鼠具有DRG神经元的一个子集的发育损失。甘丙肽还在成年动物中起营养作用，并且在成年Gal-KO小鼠中外周神经再生和神经突生长的速率降低。在这里，我们描述了小鼠的特性与GalR 2基因转录（GalR 2-MUT）的情况下，并证明他们有一个15%的降钙素基因相关肽（CGRP）表达的神经元在成人DRG的配置文件，与显着的赤字在神经性和炎症性疼痛行为减少。成年GalR 2-MUT动物也具有来自培养的DRG神经元的神经突生长的三分之一减少，其不能被甘丙肽或高亲和力GalR 2/3激动剂拯救。甘丙肽激活成年野生型（WT）小鼠DRG中的细胞外信号调节激酶（ERK）和Akt。来自GalR 2-MUT动物的完整成年DRG具有比在WT对照中发现的更低水平的pERK和更高水平的pAkt。这些数据表明，Gal-KO和GalR 2-MUT动物中GalR 2活化的缺乏是导致DRG中观察到的发育缺陷和成年神经突生长减少的原因。
Expression of the neuropeptide galanin is markedly up-regulated within the adult dorsal root ganglia (DRG) following peripheral nerve injury. We have previously demonstrated that galanin knockout (Gal-KO) mice have a developmental loss of a subset of DRG neurons. Galanin also plays a trophic role in the adult animal, and the rate of peripheral nerve regeneration and neurite outgrowth is reduced in adult Gal-KO mice. Here we describe the characterization of mice with an absence of GalR2 gene transcription (GalR2-MUT) and demonstrate that they have a 15% decrease in the number of calcitonin generelated peptide (CGRP) expressing neuronal profiles in the adult DRG, associated with marked deficits in neuropathic and inflammatory pain behaviours. Adult GalR2-MUT animals also have a one third reduction in neurite outgrowth from cultured DRG neurons that cannot be rescued by either galanin or a high-affinity GalR2/3 agonist. Galanin activates extracellular signal-regulated kinase (ERK) and Akt in adult wild-type (WT) mouse DRG. Intact adult DRG from GalR2-MUT animals have lower levels of pERK and higher levels of pAkt than are found in WT controls. These data suggest that a lack of GalR2 activation in Gal-KO and GalR2-MUT animals is responsible for the observed developmental deficits in the DRG, and the decrease in neurite outgrowth in the adult.
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DOI：
10.1074/jbc.m401281200
发表时间：
2004-06-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Kerr NC;Holmes FE;Wynick D
通讯作者：
Wynick D
DOI：
10.1073/pnas.161293598
发表时间：
2001-08-14
影响因子：
11.1
作者：
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通讯作者：
Hökefelt, T
影响因子：
3.5
作者：
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通讯作者：
SCHALLER, H
影响因子：
3.3
作者：
Hohmann, JG;Juréus, A;Steiner, RA
通讯作者：
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DOI：
10.1073/pnas.91.21.9780
发表时间：
1994-10-11
影响因子：
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作者：
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MAYAUX, JF