Elsevier

Experimental Neurology

Volume 167, Issue 2, February 2001, Pages 290-303
Experimental Neurology

Regular Article
Effect of Peripheral Nerve Lesion and Lumbar Sympathectomy on Peptide Regulation in Dorsal Root Ganglia in the NGF-Overexpressing Mouse

https://doi.org/10.1006/exnr.2000.7552Get rights and content

Abstract

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.

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      This study provides valuable information about the therapeutic potential of administration of galanin or galanin receptor 1 agonist for painful diabetic neuropathy. Galanin is normally expressed at low levels (Holmberg et al., 2001) and is markedly up-regulated in DRG and SDH following peripheral nerve injury and inflammation in the adult (Bacon et al., 2007; Hobson et al., 2006; Holmberg et al., 2005; Holmes et al., 2005; Macdonald et al., 2001; Shi et al., 2009; Zvarova and Vizzard, 2006). The expression of galanin is regulated by many nerve trophic factors and cytokines which change their level after nerve injury and inflammation, such as down regulated by nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, basic fibroblast growth factor (Kerekes et al., 1997; Shadiack et al., 2001; Wang et al., 2003; Wendland et al., 2003), and up regulated by interleukin-6, leukemia inhibitory factor (Corness et al., 1996; Murphy et al., 1999; Sun and Zigmond, 1996a,b).

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    To whom correspondence should be addressed at the Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden. Fax: +468 33 16 92. E-mail: [email protected].

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