title: Gene expression in amygdala as a function of differential trait anxiety levels in genetically heterogeneous NIH-HS rats.
abstract: To identify genes involved in anxiety/fear traits, we analyzed the gene expression profile in the amygdala of genetically heterogeneous NIH-HS rats. The NIH-HS rat stock has revealed to be a unique genetic resource for the fine mapping of Quantitative Trait Loci (QTLs) to very small genomic regions, due to the high amount of genetic recombinants accumulated along more than 50 breeding generations, and for the same reason it can be expected that those genetically heterogeneous rats should be especially useful for studying differential gene expression as a function of anxiety-(or other)-related traits. We selected high- and low-anxious NIH-HS rats differing in their number of avoidances in a single 50-trial session of the two-way active avoidance task. Rats were also tested in unconditioned anxiety tests (e.g., elevated zero-maze). Three weeks after behavioural testing, the amygdala was dissected and prepared for the microarray study. There appeared 6 significantly down-regulated and 28 up-regulated genes (fold-change >|2|, FDR<0.05) between the low- and high-anxious groups, with central nervous system-related functions. Regression analyses (stepwise) revealed that differential expression of some genes could be predictive of anxiety/fear responses. Among those genes for which the present results suggest a link with individual differences in trait anxiety, six relevant genes were examined with qRT-PCR, four of which (Ucn3, Tacr3, H2-M9 and Arr3) were validated. Remarkably, some of them are characterized by sharing known functions related with hormonal HPA-axis responses to (and/or modulation of) stress, anxiety or fear, and putative involvement in related neurobehavioural functions. The results confirm the usefulness of NIH-HS rats as a good animal model for research on the neurogenetic basis of anxiety and fear, while suggesting the involvement of some neuropeptide/neuroendocrine pathways on the development of differential anxiety profiles.
authors.affiliation: Medical Psychology Unit, Department of Psychiatry & Forensic Medicine, Institute of Neurosciences, School of Medicine, Universidad Autónoma de Barcelona, Barcelona, Spain. Sira.Diaz@uab.cat
authors.forename: Sira
authors.initials: S
authors.lastname: Díaz-Morán
authors.forename: Marta
authors.initials: M
authors.lastname: Palència
authors.forename: Carme
authors.initials: C
authors.lastname: Mont-Cardona
authors.forename: Toni
authors.initials: T
authors.lastname: Cañete
authors.forename: Gloria
authors.initials: G
authors.lastname: Blázquez
authors.forename: Esther
authors.initials: E
authors.lastname: Martínez-Membrives
authors.forename: Regina
authors.initials: R
authors.lastname: López-Aumatell
authors.forename: Marta
authors.initials: M
authors.lastname: Sabariego
authors.forename: Rocío
authors.initials: R
authors.lastname: Donaire
authors.forename: Ignacio
authors.initials: I
authors.lastname: Morón
authors.forename: Carmen
authors.initials: C
authors.lastname: Torres
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Martínez-Conejero
authors.forename: Adolf
authors.initials: A
authors.lastname: Tobeña
authors.forename: Francisco José
authors.initials: FJ
authors.lastname: Esteban
authors.forename: Alberto
authors.initials: A
authors.lastname: Fernández-Teruel
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D001362:Avoidance Learning / Q000502:physiology; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D018740:Genetic Heterogeneity; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009043:Motor Activity / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D040641:Quantitative Trait Loci / Q000235:genetics*; D051381:Rats; D013216:Reflex, Startle / Q000235:genetics; D012044:Regression Analysis; D018709:Statistics, Nonparametric
keywords: Amygdala; Anxiety trait; Fearfulness; Genetically heterogeneous NIH-HS rats; HPA-axis; Microarray analysis