Neuronal UCPs are induced by oxidative stress products and by superoxide and seem to be crucial for reducing the mitochondrial ROS production. The present paper is aimed at further investigating the neuroprotective effects of UCPs in fish brain, especially with respect to how UCPs are controlled under cold-induced oxidative stress in the fish CNS. The physiological role of PPARs in UCP gene expression and the mechanism of PPARs in the prevention of oxidative stress and neuroprotection have been reported in mammals. One of these studies suggests that UCPs may be involved in PPAR dependent gene transactivation through intrachromosomal looping next to their uncoupling function in the mitochondria. Another important transcription factor involved in temperature control of gene transcription, although via an indirect effect of temperature induced hypoxia, is the hypoxia inducible factor HIF-1. HIF-1 protein stabilization was observed in temperate eelpout during GANT61 winter cold. Parallel UCP2 was upregulated in cold adapted eelpout. In addition, ROS over production in CNS caused the expressions of HIF-1 responsive genes, such as glucose transporters, vascular endothelial growth factor, and erythropoietin, for supporting ATP production and facilitating oxygen supply. There is considerable evidence supporting the issue of bidirectional crosstalk between mitochondrial ROS and HIF activity. These ROS may act as signaling molecules that somehow influence the regulation of the HIF pathway during hypoxia. Although the response to cold challenge in teleost fish has been intensively studied, the molecular and physiological mechanisms and mutual relations protecting fish CNS against cold induced ROS damage are not at all understood. Therefore, particular attention should be paid on the regulatory aspects of gene transcription, involving HIF and the PPAR/UCP system. Moreover, the CNS cellular metabolism modulation should also be examined. In the present study we used the warm adapted zebrafish model, Danio rerio, to study the effects of acute cold exposure on fish brain. The zebrafish model is backed by a genetic database, and its applicability to study various molecular/cellular pathways and pathologies has been confirmed. UCP AB1010 VEGFR/PDGFR inhibitor homologs in zebrafish were explored from genomic sequence analysis to transcript expressions. Specifically, we have, for the first time, measured the expression levels of UCP/PPAR, an oxidative stress parameter and several antioxidative parameters in the CNS of zebrafish upon acute cold exposure. In addition, HIF-1a protein content and the transcript levels of HIF-regulated GLUTs were quantified to test for an involvement of UCPs and HIF in modulating stress during cold exposure in fish brain. Multiple sequence alignment and phylogenetic analysis with homologues of other species clearly identified 5 members of the zUCP family which enables unambiguous identification of the zebrafish homologues.