Oxidative stress, neuroendocrine function and behavior in an animal model of extended longevity

Leiden Repository

Oxidative stress, neuroendocrine function and behavior in an animal model of extended longevity

Type: Doctoral Thesis
Title: Oxidative stress, neuroendocrine function and behavior in an animal model of extended longevity
Author: Berry, Alessandra
Publisher: Department of Neuropharmacology, Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Issue Date: 2010-04-21
Keywords: p66Shc
Aging
Hypothalamic-pituitary-adrenal axis (HPA)
Mice
Oxidative stress
Behaviour
Animal model
Lifespan
Healthspan
Abstract: Stress and oxidative stress (OS) might act synergistically to exacerbate the neuronal decay associated with aging. Recent evidence has shown a redox regulation of the function of the glucocorticoid receptors as nuclear transcription factors. The lack of the p66Shc gene reduces OS and increases lifespan in mice. Main aim of the study was to elucidate whether the interactions linking OS and the neuroendocrine system represent a crucial determinant of aging in p66Shc-/- mice. Thus, the contribution of p66Shc to behaviour and neuroendocrine regulations was assessed from early post-natal life to senescence. Mutant old mice were characterized by a slow-down in physical and emotional aging; adult subjects showed increased behavioural plasticity and lower emotionality associated to increased central levels of Brain-derived neurotrophic factor, reduced oxidative stress markers and greater resilience to stress-induced changes in the internal milieu. A role has been recently described for p66Shc in regulating energetic metabolism. Intriguingly, we found metabolic and emotional aspects to be strictly related and possibly mediated by maternal behaviour in these mutants. Our results shed light on the role played by OS and metabolism in longevity and emotionality/mood disorders and point to p66Shc as a candidate gene in the trade-off between fertility and lifespan.
Description: Promotor: E.R. de Kloet, Co-promotor: F. Cirulli
With Summary in Dutch
Faculty: LUMC
Citation: Berry, A., 2010, Doctoral Thesis, Leiden University
ISBN: 9789074538725
Handle: http://hdl.handle.net/1887/15280
 

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application/pdf Chapter 1 262.4Kb View/Open
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application/pdf Summary in English 30.42Kb View/Open
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application/pdf Curriculum Vitae_Publications_Acknowledgements 44.11Kb View/Open
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