title: Trib3 is developmentally and nutritionally regulated in the brain but is dispensable for spatial memory, fear conditioning and sensing of amino acid-imbalanced diet.
abstract: Tribbles homolog 3 (TRIB3) is a mammalian pseudokinase that is induced in neuronal cell cultures in response to cell death-inducing stresses, including neurotrophic factor deprivation. TRIB3 is an inhibitor of activating transcription factor 4 (ATF4), the central transcriptional regulator in the eukaryotic translation initiation factor 2α (eIF2α) phosphorylation pathway that is involved in the cellular stress response and behavioral processes. In this article, we study the expression of Trib3 in the mouse brain, characterize the brain morphology of mice with a genetic ablation of Trib3 and investigate whether Trib3 deficiency alters eIF2α-dependent cognitive abilities. Our data show that the consumption of a leucine-deficient diet induces Trib3 expression in the anterior piriform cortex, the brain region responsible for detecting essential amino acid intake imbalance. However, the aversive response to leucine-devoid diet does not differ in Trib3 knockout and wild type mice. Trib3 deletion also does not affect long-term spatial memory and reversal learning in the Morris water maze and auditory or contextual fear conditioning. During embryonic development, Trib3 expression increases in the brain and persists in the early postnatal stadium. Neuroanatomical characterization of mice lacking Trib3 revealed enlarged lateral ventricles. Thus, although the absence of Trib3 does not alter the eIF2α pathway-dependent cognitive functions of several areas of the brain, including the hippocampus, amygdala and anterior piriform cortex, Trib3 may serve a role in other central nervous system processes and molecular pathways.
authors.affiliation: Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Tiit
authors.initials: T
authors.lastname: Örd
authors.affiliation: Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Innos
authors.affiliation: Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia; Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
authors.forename: Kersti
authors.initials: K
authors.lastname: Lilleväli
authors.affiliation: Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
authors.forename: Triin
authors.initials: T
authors.lastname: Tekko
authors.affiliation: Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
authors.forename: Silva
authors.initials: S
authors.lastname: Sütt
authors.affiliation: Estonian Biocentre, Tartu, Estonia.
authors.forename: Daima
authors.initials: D
authors.lastname: Örd
authors.affiliation: Chair of Pathological Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
authors.forename: Sulev
authors.initials: S
authors.lastname: Kõks
authors.affiliation: Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
authors.forename: Eero
authors.initials: E
authors.lastname: Vasar
authors.affiliation: Estonian Biocentre, Tartu, Estonia.
authors.forename: Tõnis
authors.initials: T
authors.lastname: Örd
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003214:Conditioning, Classical; D004032:Diet; D005239:Fear; D017353:Gene Deletion; D005786:Gene Expression Regulation; D007930:Leucine / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D015398:Signal Transduction; D065852:Spatial Memory
chemical_list: D000596:Amino Acids; D018797:Cell Cycle Proteins; C474830:TRB3 protein, mouse; D007930:Leucine
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