title: The cytokine ciliary neurotrophic factor (CNTF) activates hypothalamic urocortin-expressing neurons both in vitro and in vivo.
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.
authors.affiliation: Department of Physiology, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Purser
authors.forename: Prasad S
authors.initials: PS
authors.lastname: Dalvi
authors.forename: Zi C
authors.initials: ZC
authors.lastname: Wang
authors.forename: Denise D
authors.initials: DD
authors.lastname: Belsham
mesh_terms: D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001066:Appetite / Q000187:drug effects / Q000502:physiology; D001067:Appetite Depressants / Q000378:metabolism / Q000494:pharmacology*; D001069:Appetite Regulation / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009496:Neurotensin / Q000235:genetics / Q000378:metabolism; D020801:Receptor, Ciliary Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D054832:Urocortins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism
chemical_list: D054369:Agouti-Related Protein; D001067:Appetite Depressants; D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D020801:Receptor, Ciliary Neurotrophic Factor; C549377:Ucn1 protein, mouse; D054832:Urocortins; C518358:urocortin 2, mouse; D009496:Neurotensin; D003346:Corticotropin-Releasing Hormone