Phenotyping of sensory and sympathetic ganglion neurons of a galanin-overexpressing mouse--possible implications for pain processing.
The distribution of galanin was studied in the lumbar 5 dorsal root ganglia (DRGs) and spinal cord, superior cervical ganglia (SCGs), and skin of transgenic mice overexpressing galanin under the dopamine beta-hydroxylase (DBH) promoter (GalOE-DBH mice) and in wild type (WT) mice. The DRGs and spinal cord were analysed before and after a unilateral, complete transection (axotomy) of the sciatic nerve and after dorsal rhizotomy. Both galanin protein and transcript were studied by, respectively, immunohistochemistry and in situ hybridization. Increased galanin expression was observed in several small, medium-sized and large DRG neuron profiles (NPs) in the naïve transgenic mouse, frequently in neurons lacking calcitonin gene-related peptide (CGRP) and isolectin B4-binding. This lack of coexistence was particularly evident in the medium-sized/large NPs. In the dorsal horn of the spinal cord, no differences were detected between GalOE-DBH and WT mice, both displaying a strong galanin-positive neuropil in the superficial laminae of the dorsal horn, but the transgenic mice showed a more abundant galanin-positive innervation of the ventral horn. A 12-day dorsal rhizotomy, surprisingly, failed to alter the galanin staining patterns in the dorsal (and ventral) dorsal horn. Unilateral axotomy induced upregulation of galanin in DRG NPs of all sizes in both types of mouse. In the hindpaw skin, a profuse galanin-positive fiber plexus was observed in sweat glands and around blood vessels of the transgenic mice, being much more restricted in WT mice. Finally, GalOE mice exhibited a strong galanin-like immunoreactivity in most SCG NPs. The overexpression of the peptide in DRGs and SCGs was paralleled by increased mRNA levels. The present results show that overexpression of galanin under the control of the DBH promoter does not only occur, as expected in these mice, in noradrenline/adrenaline neurons but also in DRG neurons, particularly in large and medium-sized NPs. To what extent and how this overexpression pattern is related to the previously shown elevated pain threshold under normal and lesion conditions is discussed [Grass, S., Crawley, J.N., Xu, X.J., Wiesenfeld-Hallin, Z., 2003a. Reduced spinal cord sensitization to C-fibre stimulation in mice over-expressing galanin. Eur. J. Neurosci. 17, 1829-1832; Hygge-Blakeman, K., Brumovsky, P., Hao, J.X., Xu, X.J., Hökfelt, T., Crawley, J.N., Wiesenfeld-Hallin, Z., 2004. Galanin over-expression decreases the development of neuropathic pain-like behaviour in mice after partial sciatic nerve injury. Brain Res. 1025, 152-158].
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Pablo_Brumovsky@yahoo.com
Pablo
P
Brumovsky
Karin
K
Hygge-Blakeman
Marcelo J
MJ
Villar
Masahiko
M
Watanabe
Zsuzsanna
Z
Wiesenfeld-Hallin
Tomas
T
Hökfelt
D000818:Animals; D019771:Axotomy; D004195:Disease Models, Animal; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D019004:Galanin / Q000235:genetics* / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010146:Pain / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D010641:Phenotype; D020671:Posterior Horn Cells / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D019051:Rhizotomy; D020426:Sciatic Neuropathy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011984:Sensory Receptor Cells / Q000378:metabolism; D012867:Skin / Q000294:innervation; D015854:Up-Regulation / Q000502:physiology
D012333:RNA, Messenger; D019004:Galanin; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine