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Early dysfunction of central 5-HT system in a murine model of bovine spongiform encephalopathy

Academic Article
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Overview

authors

  • Vidal, C.
  • Herzog, C.
  • Haeberle, A. M.
  • Bombarde, C.
  • Miquel, M. C.
  • Carimalo, J.
  • Launay, J. M.
  • Mouillet-Richard, S.
  • Lasmezas, Corinne
  • Dormont, D.
  • Kellermann, O.
  • Bailly, Y.

publication date

  • June 2009

journal

  • Neuroscience  Journal

abstract

  • The hypothesis of an early vulnerability of the serotonergic system to prion infection was investigated in a murine model of bovine spongiform encephalopathy (BSE). Behavioral tests targeted to 5-HT functions were performed in the course of infection to evaluate circadian activity, anxiety-like behavior, pain sensitivity and the 5-HT syndrome. The first behavioral change was a decrease in nocturnal activity detected at 30% of incubation time. Further behavioral alterations including nocturnal hyperactivity, reduced anxiety, hyperalgesia and exaggerated 5-HT syndrome were observed at 60%-70% of incubation time, before the onset of clinical signs. The same tests performed in 5-HT-depleted mice and in prion protein-deficient mice revealed behavioral abnormalities similar in many aspects to those of BSE-infected mice. Histological and biochemical analysis showed alterations of the serotonergic system in BSE-infected and prion protein-deficient mice. These results indicate that BSE infection affects the homeostasis of serotonergic neurons and suggest that the disruption of prion protein normal function contributes to the early pathological changes in our mouse model of BSE. A similar process may occur in the human variant Creutzfeldt-Jacob disease, as suggested by the early symptoms of alterations in mood, sleep and pain sensitivity.

subject areas

  • Animals
  • Anxiety Disorders
  • Brain
  • Brain Stem
  • Cattle
  • Chronobiology Disorders
  • Disease Models, Animal
  • Disease Progression
  • Encephalopathy, Bovine Spongiform
  • Female
  • Homeostasis
  • Mental Disorders
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons
  • Pain
  • PrPC Proteins
  • PrPSc Proteins
  • Raphe Nuclei
  • Serotonin
  • Serotonin Syndrome
  • Time Factors
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Research

keywords

  • 5-HT
  • BSE
  • neurodegenerative disease
  • prion
  • raphe
  • suprachiasmatic nucleus
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Identity

International Standard Serial Number (ISSN)

  • 0306-4522

Digital Object Identifier (DOI)

  • 10.1016/j.neuroscience.2009.02.072

PubMed ID

  • 19285121
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Additional Document Info

start page

  • 731

end page

  • 743

volume

  • 160

issue

  • 4

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