title: Endogenous ciliary neurotrophic factor modulates anxiety and depressive-like behavior.
abstract: On a molecular level, depression is characterized by an altered monoaminergic neurotransmission as well as a modulation of cytokines and other mediators in the central nervous system. In particular, neurotrophic factors may influence affective behavior including depression and anxiety. Ciliary neurotrophic factor (CNTF) plays an important role in the regulation of neuronal development, neuroprotection and may also influence cognitive processes. Here we investigate the affective behavior in mice deficient for CNTF (CNTF -/- mice) at young age of 10-20 weeks. CNTF -/- mice displayed an increased anxiety-like behavior with a 30% reduction of the time spent in the bright compartment of the light/dark box as well as a significantly increased startle response. In the learned helplessness paradigm, CNTF -/- mice are more prone to depressive-like behavior. In the hippocampus of 20 weeks old, but not 10 weeks old, CNTF -/- mice, these changes correlated with a loss of parvalbumin immunoreactive GABAergic interneurons and a reduction of serotonin levels as well as 5-HT receptor 1A expression. Modulation of monoaminergic neurotransmitter levels via chronic application of the antidepressants amitriptyline and citalopram did not exert beneficial effects. These data imply that endogenous CNTF plays a pivotal role for the structural maintenance of hippocampal functions and thus has an important impact on the modulation of affective behavior in rodent models of anxiety and depression.
authors.affiliation: Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Universitätsstr. 150, Bochum, Germany.
authors.forename: Isabella
authors.initials: I
authors.lastname: Peruga
authors.forename: Silvia
authors.initials: S
authors.lastname: Hartwig
authors.forename: Doron
authors.initials: D
authors.lastname: Merkler
authors.forename: Jan
authors.initials: J
authors.lastname: Thöne
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hovemann
authors.forename: Georg
authors.initials: G
authors.lastname: Juckel
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Linker
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D015306:Biogenic Monoamines / Q000378:metabolism; D002452:Cell Count / Q000706:statistics & numerical data; D020934:Ciliary Neurotrophic Factor / Q000235:genetics / Q000502:physiology*; D015283:Citalopram / Q000494:pharmacology; D003863:Depression / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D059330:GABAergic Neurons / Q000378:metabolism; D006380:Helplessness, Learned; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007395:Interneurons / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D009048:Motor Skills / Q000502:physiology; D044282:Receptor, Serotonin, 5-HT1A / Q000096:biosynthesis; D045442:Rotarod Performance Test / Q000379:methods; D055139:Sensory Gating / Q000235:genetics / Q000502:physiology
chemical_list: D015306:Biogenic Monoamines; D020934:Ciliary Neurotrophic Factor; D015283:Citalopram; D044282:Receptor, Serotonin, 5-HT1A; D000639:Amitriptyline