Holmberg K, Shi T J, Albers K M, Davis B M, Hökfelt T
Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Exp Neurol. 2001 Feb;167(2):290-303. doi: 10.1006/exnr.2000.7552.
Galanin is a peptide normally expressed at low levels both in sensory and in sympathetic neurons. It is strongly upregulated after peripheral nerve lesions, and it has been proposed that nerve growth factor (NGF) plays a role in this regulation. In the present study the effect of both sciatic nerve transection and lumbar sympathectomy on galanin in lumbar dorsal root ganglia (DRGs) was examined in mice overexpressing NGF (NGFOE) in the skin under the keratin promoter. The superior cervical ganglia (SCG) were also studied. In the DRG pericellular baskets containing tyrosine hydroxylase- (TH) and galanin-like immunoreactivity (LI) were found, mostly in the same fibers. Galanin-positive baskets were also found in the trigeminal ganglia. However, only single neuropeptide Y (NPY)-positive baskets were observed within the DRGs. No marked difference in number of galanin-positive neurons was seen between wild-type and NGFOE mice. After sciatic nerve transection galanin was upregulated in DRG neurons to about the same extent in NGFOE mice as in wild-type mice. Galanin-, but not TH-LIs decreased in the pericellular baskets. After lumbar sympathectomy both galanin- and TH-immunoreactive baskets disappeared, suggesting a sympathetic origin. In the SCG the very low galanin mRNA levels were strongly increased after lesion of the carotid nerves, both in wild-type and in NGFOE mice. However, whereas NPY mRNA levels decreased in the SCG after axotomy in the wild-type mice, there was a distinct increase in the NGFOE mice. Our results show that high NGF levels in skin induce formation of pericellular baskets in DRGs expressing galanin- and TH-LI and that galanin in these baskets is strongly influenced by peripheral axotomy. However, overexpression of NGF did not markedly influence galanin expression in DRG neurons, neither normally nor after nerve lesions. Finally, expression of NPY in sympathetic ganglia is differently regulated in NGFOE compared to wild-type mice.
甘丙肽是一种通常在感觉神经元和交感神经元中低水平表达的肽。在外周神经损伤后它会强烈上调,有人提出神经生长因子(NGF)在这种调节中起作用。在本研究中,在角蛋白启动子驱动下皮肤中过表达NGF(NGFOE)的小鼠身上,检测了坐骨神经横断和腰交感神经切除术对腰背根神经节(DRG)中甘丙肽的影响。还研究了颈上神经节(SCG)。在DRG中发现了含有酪氨酸羟化酶(TH)和甘丙肽样免疫反应性(LI)的细胞周篮,大多在同一纤维中。在三叉神经节中也发现了甘丙肽阳性篮。然而,在DRG内仅观察到单个神经肽Y(NPY)阳性篮。野生型小鼠和NGFOE小鼠之间甘丙肽阳性神经元数量未见明显差异。坐骨神经横断后,DRG神经元中的甘丙肽在NGFOE小鼠中上调程度与野生型小鼠大致相同。细胞周篮中甘丙肽免疫反应性降低,但TH免疫反应性未降低。腰交感神经切除术后,甘丙肽和TH免疫反应性篮均消失,提示其起源于交感神经。在SCG中,野生型小鼠和NGFOE小鼠在颈动脉神经损伤后,极低的甘丙肽mRNA水平均强烈升高。然而,野生型小鼠轴突切断后SCG中NPY mRNA水平降低,而NGFOE小鼠中则明显升高。我们的结果表明,皮肤中高NGF水平诱导表达甘丙肽和TH-LI的DRG中形成细胞周篮,且这些篮中的甘丙肽受外周轴突切断的强烈影响。然而,NGF过表达在正常情况下或神经损伤后均未显著影响DRG神经元中甘丙肽的表达。最后,与野生型小鼠相比,NGFOE小鼠交感神经节中NPY的表达受到不同调节。