Neuronal activity and axonal sprouting differentially regulate CNTF and CNTF receptor complex in the rat supraoptic nucleus

Exp Neurol. 2012 Jan;233(1):243-52. doi: 10.1016/j.expneurol.2011.10.009. Epub 2011 Oct 19.

Abstract

We demonstrated previously that the hypothalamic supraoptic nucleus (SON) undergoes a robust axonal sprouting response following unilateral transection of the hypothalamo-neurohypophysial tract. Concomitant with this response is an increase in ciliary neurotrophic factor (CNTF) and CNTF receptor alpha (CNTFRα) expression in the contralateral non-uninjured SON from which the axonal outgrowth occurs. While these findings suggest that CNTF may act as a growth factor in support of neuronal plasticity in the SON, it remained to be determined if the observed increase in neurotrophin expression was related to the sprouting response per se or more generally to the increased neurosecretory activity associated with the post-lesion response. Therefore we used immunocytochemistry and Western blot analysis to examine the expression of CNTF and the components of the CNTF receptor complex in sprouting versus osmotically-stimulated SON. Western blot analysis revealed a significant increase in CNTF, CNTFRα, and gp130, but not LIFRß, protein levels in the sprouting SON at 10days post lesion in the absence of neuronal loss. In contrast, osmotic stimulation of neurosecretory activity in the absence of injury resulted in a significant decrease in CNTF protein levels with no change in CNTFRα, gp130, or LIFRß protein levels. Immunocytochemical analysis further demonstrated gp130 localization on magnocellular neurons and astrocytes while the LIFRß receptor was found only on astrocytes in the SON. These results are consistent with the hypothesis that increased CNTF and CNTFR complex in the sprouting, metabolically active SON are related directly to the sprouting response and not the increase in neurosecretory activity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Axons / drug effects
  • Axons / physiology*
  • Ciliary Neurotrophic Factor / metabolism*
  • Cytokine Receptor gp130 / metabolism
  • Gene Expression Regulation
  • Glial Fibrillary Acidic Protein / metabolism
  • Male
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology*
  • Oxytocin / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Ciliary Neurotrophic Factor / metabolism*
  • Regeneration / physiology*
  • Salts / administration & dosage
  • Supraoptic Nucleus / injuries
  • Supraoptic Nucleus / pathology*
  • Time Factors
  • Vasopressins / metabolism

Substances

  • Ciliary Neurotrophic Factor
  • Glial Fibrillary Acidic Protein
  • Receptor, Ciliary Neurotrophic Factor
  • Salts
  • Vasopressins
  • Cytokine Receptor gp130
  • Oxytocin