The cytokine ciliary neurotrophic factor (CNTF) activates hypothalamic urocortin-expressing neurons both in vitro and in vivo

PLoS One. 2013 Apr 23;8(4):e61616. doi: 10.1371/journal.pone.0061616. Print 2013.

Abstract

Ciliary neurotrophic factor (CNTF) induces neurogenesis, reduces feeding, and induces weight loss. However, the central mechanisms by which CNTF acts are vague. We employed the mHypoE-20/2 line that endogenously expresses the CNTF receptor to examine the direct effects of CNTF on mRNA levels of urocortin-1, urocortin-2, agouti-related peptide, brain-derived neurotrophic factor, and neurotensin. We found that treatment of 10 ng/ml CNTF significantly increased only urocortin-1 mRNA by 1.84-fold at 48 h. We then performed intracerebroventricular injections of 0.5 mg/mL CNTF into mice, and examined its effects on urocortin-1 neurons post-exposure. Through double-label immunohistochemistry using specific antibodies against c-Fos and urocortin-1, we showed that central CNTF administration significantly activated urocortin-1 neurons in specific areas of the hypothalamus. Taken together, our studies point to a potential role for CNTF in regulating hypothalamic urocortin-1-expressing neurons to mediate its recognized effects on energy homeostasis, neuronal proliferaton/survival, and/or neurogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti-Related Protein / genetics
  • Agouti-Related Protein / metabolism
  • Animals
  • Appetite / drug effects
  • Appetite / physiology
  • Appetite Depressants / metabolism
  • Appetite Depressants / pharmacology*
  • Appetite Regulation / drug effects
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Line
  • Ciliary Neurotrophic Factor / metabolism
  • Ciliary Neurotrophic Factor / pharmacology*
  • Corticotropin-Releasing Hormone / genetics
  • Corticotropin-Releasing Hormone / metabolism
  • Gene Expression Regulation / drug effects
  • Hypothalamus / cytology
  • Hypothalamus / drug effects*
  • Hypothalamus / metabolism
  • Injections, Intraventricular
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurotensin / genetics
  • Neurotensin / metabolism
  • Receptor, Ciliary Neurotrophic Factor / genetics
  • Receptor, Ciliary Neurotrophic Factor / metabolism
  • Urocortins / agonists
  • Urocortins / genetics*
  • Urocortins / metabolism

Substances

  • Agouti-Related Protein
  • Appetite Depressants
  • Brain-Derived Neurotrophic Factor
  • Ciliary Neurotrophic Factor
  • Receptor, Ciliary Neurotrophic Factor
  • Ucn1 protein, mouse
  • Urocortins
  • urocortin 2, mouse
  • Neurotensin
  • Corticotropin-Releasing Hormone