Fibroblast growth factor deficiencies impact anxiety-like behavior and the serotonergic system.

Autor: Brooks LR; Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA. Electronic address: leah.brooks@colorado.edu., Enix CL; Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA., Rich SC; Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA., Magno JA; Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA., Lowry CA; Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA., Tsai PS; Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2014 May 01; Vol. 264, pp. 74-81. Date of Electronic Publication: 2014 Feb 07.
DOI: 10.1016/j.bbr.2014.01.053
Abstrakt: Serotonergic neurons in the dorsal raphe nucleus (DR) are organized in anatomically distinct subregions that form connections with specific brain structures to modulate diverse behaviors, including anxiety-like behavior. It is unclear if the functional heterogeneity of these neurons is coupled to their developmental heterogeneity, and if abnormal development of specific DR serotonergic subregions can permanently impact anxiety circuits and behavior. The goal of this study was to examine if deficiencies in different components of fibroblast growth factor (Fgf) signaling could preferentially impact the development of specific populations of DR serotonergic neurons to alter anxiety-like behavior in adulthood. Wild-type and heterozygous male mice globally hypomorphic for Fgf8, Fgfr1, or both (Fgfr1/Fgf8) were tested in an anxiety-related behavioral battery. Both Fgf8- and Fgfr1/Fgf8-deficient mice display increased anxiety-like behavior as measured in the elevated plus-maze and the open-field tests. Immunohistochemical staining of a serotonergic marker, tryptophan hydroxylase (Tph), revealed reductions in specific populations of serotonergic neurons in the ventral, interfascicular, and ventrolateral/ventrolateral periaqueductal gray subregions of the DR in all Fgf-deficient mice, suggesting a neuroanatomical basis for increased anxiety-like behavior. Overall, this study suggests Fgf signaling selectively modulates the development of different serotonergic neuron subpopulations. Further, it suggests anxiety-like behavior may stem from developmental disruption of these neurons, and individuals with inactivating mutations in Fgf signaling genes may be predisposed to anxiety disorders.
(Published by Elsevier B.V.)
Databáze: MEDLINE
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