Contribution of the Reelin signaling pathways to nociceptive processing

Alin L. Akopians, Alex H. Babayan, Uwe Beffert, Joachim Herz, Allan I. Basbaum, Patricia E. Phelps

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The reeler gene encodes Reelin, a secreted glycoprotein that binds to the very-low-density lipoprotein receptor (Vldlr) and apolipoprotein E receptor 2 (Apoer 2), and induces Src- and Fyn-mediated tyrosine phosphorylation of the intracellular adaptor protein Disabled-1 (Dab1). This Reelin-Dab1 signaling pathway regulates neuronal positioning during development. A second Reelin pathway acts through Apoer 2-exon 19 to modulate synaptic plasticity in adult mice. We recently reported positioning errors in reeler dorsal horn laminae I-II and V, and the lateral spinal nucleus. Behavioral correlates of these positioning errors include a decreased mechanical and increased thermal sensitivity in reeler mice. Here we examined mice with deletions or modifications of both the Reelin-Dab1 signaling pathway and the Reelin-Apoer 2-exon 19 pathway on a Vldlr-deficient background. We detected reeler-like dorsal horn positioning errors only in Dab1 mutant and Apoer 2/Vldlr double mutant mice. Although Dab1 mutants, like reeler, showed decreased mechanical and increased thermal sensitivity, neither the single Vldlr or Apoer 2 knockouts, nor the Apoer 2-exon 19 mutants differed in their acute pain sensitivity from controls. However, despite the dramatic alterations in acute 'pain' processing in reeler and Dab1 mutants, the exacerbation of pain processing after tissue injury (hindpaw carrageenan injection) was preserved. Finally, we recapitulated the reeler dorsal horn positioning errors by inhibiting Dab1 phosphorylation in organotypic cultures. We conclude that the Reelin-Dab1 pathway differentially contributes to acute and persistent pain, and that the plasticity associated with the Reelin-Apoer 2-exon 19 pathway is distinct from that which contributes to injury-induced enhancement of 'pain' processing.

Original languageEnglish (US)
Pages (from-to)523-537
Number of pages15
JournalEuropean Journal of Neuroscience
Volume27
Issue number3
DOIs
StatePublished - Feb 2008

Fingerprint

Exons
Acute Pain
Hot Temperature
Phosphorylation
Neurologic Mutant Mice
Pain
Neuronal Plasticity
Carrageenan
Wounds and Injuries
low density lipoprotein receptor-related protein 8
Tyrosine
Glycoproteins
Injections
Spinal Cord Dorsal Horn
VLDL receptor
Genes
Proteins

Keywords

  • Apoer 2
  • Dab1
  • Dorsal horn
  • Mouse
  • reeler
  • Spinal cord
  • Vldlr

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Contribution of the Reelin signaling pathways to nociceptive processing. / Akopians, Alin L.; Babayan, Alex H.; Beffert, Uwe; Herz, Joachim; Basbaum, Allan I.; Phelps, Patricia E.

In: European Journal of Neuroscience, Vol. 27, No. 3, 02.2008, p. 523-537.

Research output: Contribution to journalArticle

Akopians, Alin L. ; Babayan, Alex H. ; Beffert, Uwe ; Herz, Joachim ; Basbaum, Allan I. ; Phelps, Patricia E. / Contribution of the Reelin signaling pathways to nociceptive processing. In: European Journal of Neuroscience. 2008 ; Vol. 27, No. 3. pp. 523-537.
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