title: Effect of peripheral axotomy on dorsal root ganglion neuron phenotype and autonomy behaviour in neuropeptide Y-deficient mice.
abstract: The lumbar 5 (L5) dorsal root ganglia (DRGs) were studied in neuropeptide tyrosine (NPY)-deficient (-/-) and wild type (+/+) mice after unilateral sciatic nerve transection using in situ hybridization and immunohistochemistry. NPY, galanin and two NPY receptors (Y-Rs) were analyzed as well as self-mutilation behaviour (autotomy) and nociceptive thresholds. No difference between wild type and NPY-deficient mice was seen in the tail-flick or hot plate test. However, -/- mice showed a much stronger autotomy behaviour than wild type mice. NPY was not found in L5 DRGs in -/- mice, not even after axotomy. Galanin was upregulated to the same extent after axotomy in NPY-deficient and wild type mice. Y1- and Y2-R mRNAs were found mainly in small DRG neuron profiles. Both receptor mRNAs were downregulated after axotomy, to about the same extent in NPY-deficient as in wild type mice. In control and contralateral ganglia the mRNA levels of both receptors were lower in NPY-deficient mice than in wild type mice. The contralateral Y2-R mRNA levels did not reach control values in the NPY-deficient mice, as they did in the wild type mice. In both strains the Y1-R protein was decorating the somatic plasmalemma. The present results suggest that lack of NPY may cause exaggerated autotomy, a self-mutilation behaviour possibly related to pain sensation, in agreement with the described analgesic effect of NPY. Although significant differences in levels of Y1- and especially Y2-R mRNAs were observed between wild type and NPY-deficient mice, they were only moderate. These findings suggest that expression, regulation, localization and possible function of Y1- and Y2-Rs are not dependent on presence of the endogenous ligand. Also, deletion of NPY does not seem to influence the expression of the partly coexisting peptide galanin.
authors.affiliation: Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
authors.forename: T J
authors.initials: TJ
authors.lastname: Shi
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: O G
authors.initials: OG
authors.lastname: Berge
authors.forename: J C
authors.initials: JC
authors.lastname: Erickson
authors.forename: R D
authors.initials: RD
authors.lastname: Palmiter
authors.forename: T
authors.initials: T
authors.lastname: Hökfelt
mesh_terms: D000818:Animals; D019771:Axotomy; D001483:Base Sequence; D001522:Behavior, Animal / Q000502:physiology; D005260:Female; D019004:Galanin / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D009478:Neuropeptide Y / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D015345:Oligonucleotide Probes / Q000235:genetics; D017288:Pain Threshold / Q000502:physiology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D012652:Self Mutilation / Q000503:physiopathology
chemical_list: D009478:Neuropeptide Y; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; D019004:Galanin