In this previous study the impact of forced swim stress on stimul

In this previous study the impact of forced swim stress on stimulation of the HPA axis was evalu ated by the determination of corticosterone selleckchem Tofacitinib levels in the serum. In order to monitor the activation of the pituitary that responds to the CRF release, we also measured the ACTH levels. A set of animals of both strains was decapitated directly after stress expo sure at 08,00 h and at 12,00 h. The results show a clear increase for ACTH after stress in both mouse strains and at both time points selected in our study, like previously also for CORT. Thus, the pituitary as well as the adrenals responded immediately to the stressor. When animals were decapitated 4 h or 8 h after the stress, the levels of ACTH were not different from the non stressed controls, indicative of a functional negative feedback mechanism.

The levels in non stressed and stressed animals were higher at 16,00 than in the morning though, most likely due to the circadian rhythm of the mice. To reveal gene expression differences, samples from non stressed mice were compared to samples from mice that had been stressed 4 h or 8 h before decapitation. In C57BL 6J mice, 123 genes were 1. 4 fold regulated 4 h after stress and 88 genes 8 h after stress. In DBA 2J mice, 185 genes and 96 genes were regulated at the respective time points. Examples of the most interesting regulated genes are highlighted in tables 2, 3, 4, 5, In C57BL 6J mice, among the genes regulated 4 h after stress we distin guish phosphodiesterase 1C, Mitogen activated protein kinase kinase kinase kinase 3 and polymerase delta 1, catalytic subunit.

In the group of genes regulated 8 h after stress we noticed heat shock protein 1, alpha, Guanine nucleotide binding protein, alpha o and the regulator of G protein signaling 2. In DBA 2J mice, among the genes regulated 4 h after stress, mitogen activated protein kinase 3, Guanine nucleotide binding protein, alpha inhibiting 2, nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 were most striking, while among the genes regulated 8 h after stress Amyloid beta precursor protein, cyclin dependent kinase inhibitor 1B, Transcription factor 7 like 2, T cell specific, HMG box were most prominent. The reaction to stress on the transcriptome level differs between mouse strains and displays phases To gain more insight into the potential functions of the regulated genes, each set of regulated genes was sorted according to their ontology.

Genes coding for mitochondrial, biosynthetic and metabolic molecules, receptors, signal transduction molecules, transcription and mRNA processing molecules, ion channels and ion transport molecules, vesicular transport molecules and cytoskeleton components are highly represented. While the proportion of receptors and signal transduction molecules decreased between 4 h and Carfilzomib 8 h after stress, the proportion of mitochondrial, biosyn thetic and metabolic proteins increased in both mouse strains.

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