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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.

plos one

Trib3 Is Developmentally and Nutritionally Regulated in the Brain but Is Dispensable for Spatial Memory, Fear Conditioning and Sensing of Amino Acid-Imbalanced Diet