Abstract

Psychogenic stress contributes to the formation of brain pathology. Using gene expression microarrays, we analyzed the hippocampal transcriptome of mice subjected to acute and chronic social stress of different duration. The longest period of social stress altered the expression of the highest number of genes and most of the stress-induced changes in transcription were reversible after 5 days of rest. Chronic stress affected genes involved in the functioning of the vascular system (Alas2, Hbb-b1, Hba-a2, Hba-a1), injury response (Vwf, Mgp, Cfh, Fbln5, Col3a1, Ctgf) and inflammation (S100a8, S100a9, Ctla2a, Ctla2b, Lcn2, Lrg1, Rsad2, Isg20). The results suggest that stress may affect brain functions through the stress-induced dysfunction of the vascular system. An important issue raised in our work is also the risk of the contamination of brain tissue samples with choroid plexus. Such contamination would result in a consistent up- or down-regulation of genes, such as Ttr, Igf2, Igfbp2, Prlr, Enpp2, Sostdc1, 1500015O10RIK (Ecrg4), Kl, Clic6, Kcne2, F5, Slc4a5, and Aqp1. Our study suggests that some of the previously reported, supposedly specific changes in hippocampal gene expression, may be a result of the inclusion of choroid plexus in the hippocampal samples.

Highlights

  • Prolonged stress is an important risk factor for depression [1,2], anxiety [1], drug addiction [3], cardiovascular disease [4,5], ulcers [6], and cancer [7]

  • 10 genes unique for the time course analysis were significantly regulated both in animals subjected to 8 and 13 days of stress compared with the acute stress (Avp, Bst2, Dynlrb2, Fabp7, Lgals3bp, Mlf1, Prkcq, Rhod, Rnf152, Tekt1)

  • Only 10 genes unique for the time course analysis were significantly regulated both in animals subjected to 8 and 13 days of stress compared with the acute stress (Avp, Bst2, Dynlrb2, Fabp7, Lgals3bp, Mlf1, Prkcq, Rhod, Rnf152, Tekt1)

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Summary

Introduction

Prolonged stress is an important risk factor for depression [1,2], anxiety [1], drug addiction [3], cardiovascular disease [4,5], ulcers [6], and cancer [7]. Understanding of the adaptive and maladaptive responses to stressors can unravel the pathogenesis of stress-related diseases. One of the key brain areas involved in stress responses is the hippocampus, which is responsible for the consolidation and retrieval of contextual memories [8]. The relationship between stress and learning is important for several reasons. PLOS ONE | DOI:10.1371/journal.pone.0142195 November 10, 2015

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