Mice deficient for galanin receptor 2 have decreased neurite outgrowth from adult sensory neurons and impaired pain-like behaviour.
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 gene-related 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.
Hobson
Sally-Ann
SA
Department of Pharmacology at South Bristol, Bristol University, Bristol, UK.
Holmes
Fiona E
FE
Kerr
Niall C H
NC
Pope
Robert J P
RJ
Wynick
David
D
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D015153:Blotting, Western; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005838:Genotype; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016501:Neurites / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology*; D010146:Pain / Q000235:genetics* / Q000523:psychology*; D059348:Peripheral Nerve Injuries; D010641:Phenotype; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D044092:Receptor, Galanin, Type 2 / Q000235:genetics* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic
D012333:RNA, Messenger; D044092:Receptor, Galanin, Type 2; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases