Abstract |
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.
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Authors | Sally-Ann Hobson, Fiona E Holmes, Niall C H Kerr, Robert J P Pope, David Wynick |
Journal | Journal of neurochemistry
(J Neurochem)
Vol. 99
Issue 3
Pg. 1000-10
(Nov 2006)
ISSN: 0022-3042 [Print] England |
PMID | 17076662
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- RNA, Messenger
- Receptor, Galanin, Type 2
- Proto-Oncogene Proteins c-akt
- Extracellular Signal-Regulated MAP Kinases
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Topics |
- Animals
- Behavior, Animal
(physiology)
- Blotting, Western
- Extracellular Signal-Regulated MAP Kinases
(metabolism)
- Genotype
- Immunohistochemistry
- Male
- Mice
- Mice, Knockout
- Neurites
(physiology)
- Neurons, Afferent
(physiology)
- Pain
(genetics, psychology)
- Peripheral Nerve Injuries
- Phenotype
- Phosphorylation
- Proto-Oncogene Proteins c-akt
(physiology)
- RNA, Messenger
(biosynthesis, genetics)
- Receptor, Galanin, Type 2
(genetics, physiology)
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction
(genetics, physiology)
- Transcription, Genetic
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