Abstract Evidence has been accumulating that long-term exercise is beneficial across a range of biological systems. Research in rodents has shown that exercise reduces anxiety and impulsivity in behavioural tests. Psychological stress has been shown to evoke phospho-acetylation of histone H3 (H3S10pK14ac) and c-Fos induction at the dentate gyrus (DG). Our group has delineated the signalling pathway underlying this stress- activated sparse population of DG neurons; the ERK MAPK cascade, histone modifying enzymes and transcription factors all play a role. Interruption of any part of this pathway leads to blockade of c-Fos induction and an inability to acquire behavioural adaptation in a forced swim retest. We set out to investigate exercise- induced epigenetic, gene expression and cytoarchitecture changes at the DG, together with their underlying signalling mechanisms after stress. We employed BrdU injections to compare DG proliferation rates in running and sedentary animals but did not uncover any cytoarchitecture differences between these groups. We did find differential epigenetic and gene expression responses, however. Exercised rats were less anxious during novel environment exposure and had better memory of a forced swim stress. They had attenuated levels of pERK 112-, pMSKl and c-Fos-1R exclusively at the DG after stress, compared with sedentary controls. In terms of H3S10pK14ac-IR, exercised animals showed differential responses to sedentary controls. In general, attenuation of the stress-activated population of DG neurons could reflect the prevailing anxiety state of the animal. Lowered anxiety levels of exercised animals during novelty exposure correspond with attenuated corticosterone levels and reduced c-Fos-, pERK 1 12-, and pMSKI-IR levels at the DG. Given that the DG has a pivotal role in mnemonic-encoding, long-term voluntary exercise-induced changes in ERK MAPK signalling, epigenetic and gene expression responses could underlie improved cognition.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:555633 |
| Date | January 2011 |
| Creators | Collins, Andrew |
| Publisher | University of Bristol |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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