Distribution and neurochemical identification of pancreatic afferents in the mouse.

Distribution and neurochemical identification of pancreatic afferents in the mouse.
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DOI:
10.1002/cne.21736
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发表时间:
2008-07-01
影响因子:
2.5
通讯作者:
Davis, Brian M.
Davis, Brian M.
中科院分区:
医学3区
文献类型:
--
作者:
Fasanella, Kenneth E.;Christianson, Julie A.;Chanthaphavong, R. Savanh;Davis, Brian M.

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胰腺初级传入神经功能障碍已被证明有助于急性和慢性胰腺炎期间疼痛症状的发展。为研究胰腺传入神经的分布和神经化学表型,将Alexa Fluoro标记的霍乱毒素B(CT B)注射到成年雄性小鼠的胰头(CT B-488)和胰尾(CT B-555),逆行标记背根神经节(DRG)和结状神经节(NG)的神经元。将NG和DRG(T5-T13)进行荧光免疫组织化学处理,并通过使用共聚焦显微镜进行可视化。从T5到T13观察到脊髓胰腺传入,其中来自T9-T12的贡献最大。胰腺传入神经在左右脊神经节之间均匀分布,但左侧NG的神经支配明显大于右侧。对于脊髓和迷走神经传入有显着更大的胰头相对于尾部的神经支配。背根神经节中逆行标记的传入神经的总数与背根神经节的传入神经的总数非常相似。DRG神经元的神经化学表型主要为瞬时受体电位香草素1(TRPV 1)阳性神经元(75%)、GDNF家族受体α 3(GFRα3)阳性神经元(67%)和降钙素基因相关肽(CGRP)阳性神经元(65%)。在NG中,TRPV 1-、GFRα3-和CGRP-阳性神经元分别仅占标记传入神经元的35%、1%和15%。NG和DRG中胰腺传入神经之间的肽和受体表达的差异表明,即使它们向胰腺贡献了相似数量的初级传入神经,这两个群体在其伤害性特性和生长因子依赖性方面可能不同。
Dysfunction of primary afferents innervating the pancreas has been shown to contribute to the development of painful symptoms during acute and chronic pancreatitis. To investigate the distribution and neurochemical phenotype of pancreatic afferents, Alexa Fluor-conjugated cholera toxin B (CTB) was injected into the pancreatic head (CTB-488) and tail (CTB-555) of adult male mice to label neurons retrogradely in both the dorsal root ganglia (DRG) and nodose ganglia (NG). The NG and DRG (T5–T13) were processed for fluorescent immunohistochemistry and visualized by using confocal microscopy. Spinal pancreatic afferents were observed from T5 to T13, with the greatest contribution coming from T9–T12. The pancreatic afferents were equally distributed between right and left spinal ganglia; however, the innervation from the left NG was significantly greater than from the right. For both spinal and vagal afferents there was significantly greater innervation of the pancreatic head relative to the tail. The total number of retrogradely labeled afferents in the nodose was very similar to the total number of DRG afferents. The neurochemical phenotype of DRG neurons was dominated by transient receptor potential vanilloid 1 (TRPV1)-positive neurons (75%), GDNF family receptor alpha-3 (GFRα3)-positive neurons (67%), and calcitonin gene-related peptide (CGRP)-positive neurons(65%) neurons. In the NG, TRPV1-, GFRα3-, and CGRP-positive neurons constituted only 35%, 1%, and 15% of labeled afferents, respectively. The disparity in peptide and receptor expression between pancreatic afferents in the NG and DRG suggests that even though they contribute a similar number of primary afferents to the pancreas, these two populations may differ in regard to their nociceptive properties and growth factor dependency.
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