Elsevier

NeuroImage

Volume 17, Issue 3, November 2002, Pages 1256-1265
NeuroImage

Regular Article
Brain Regions Involved in Fatigue Sensation: Reduced Acetylcarnitine Uptake into the Brain

https://doi.org/10.1006/nimg.2002.1260Get rights and content

Abstract

Fatigue is an indispensable sense for ordering rest. However, the neuronal and molecular mechanisms of fatigue remain unclear. Chronic fatigue syndrome (CFS) with long-lasting fatigue sensation seems to be a good model for studying these mechanisms underlying fatigue sensation. Recently, we found that most patients with CFS showed a low level of serum acetylcarnitine, which well correlated with the rating score of fatigue, and that a considerable amount of acetyl moiety of serum acetylcarnitine is taken up into the brain. Here we show by metabolite analysis of the mouse brain that an acetyl moiety taken up into the brain through acetylcarnitine is mainly utilized for the biosynthesis of glutamate. When we studied the cerebral uptake of acetylcarnitine by using [2-11C]acetyl-l-carnitine in 8 patients with CFS and in 8 normal age- and sex-matched controls, a significant decrease was found in several regions of the brains of the patient group, namely, in the prefrontal (Brodmann's area 9/46d) and temporal (BA21 and 41) cortices, anterior cingulate (BA24 and 33), and cerebellum. These findings suggest that the levels of biosynthesis of neurotransmitters through acetylcarnitine might be reduced in some brain regions of chronic fatigue patients and that this abnormality might be one of the keys to unveiling the mechanisms of the chronic fatigue sensation.

References (39)

  • S. Schlegel et al.

    Regional cerebral blood flow in depression: Associations with psychopathology

    J. Affect. Disord.

    (1989)
  • A.L. Shug et al.

    The distribution and role of carnitine in the mammalian brain

    Life Sci.

    (1982)
  • U. Tirelli et al.

    Brain positron emission tomography (PET) in chronic fatigue syndrome: Preliminary data

    Am. J. Med.

    (1998)
  • K.J. Worsley et al.

    Tests for distributed, nonfocal brain activations

    Neuroimage

    (1995)
  • K. Yamaguti et al.

    Acylcarnitine metabolism during fasting and after refeeding

    Biochem. Biophys. Res. Commun.

    (1996)
  • J.L.R. Andersson et al.

    Brain networks affected by synchronized sleep visualized by positron emission tomography

    J. Cereb. Blood Flow Metab.

    (1998)
  • C.J. Bench et al.

    The anatomy of melancholia—Focal abnormalities of cerebral blood flow in major depression

    Psychol. Med.

    (1992)
  • C.J. Bench et al.

    Changes in regional cerebral blood flow on recovery from depression

    Psychol. Med.

    (1995)
  • D.C. Costa et al.

    Brainstem perfusion is impaired in chronic fatigue syndrome

    QJM

    (1995)
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    To whom correspondence and reprint requests should be addressed: Dr. Hirohiko Kuratsune, Fax: +81-6-6879-3879; E-mail: [email protected]; or Prof. Yasuyoshi Watanabe, Fax: +81-6-6645-3712; E-mail: [email protected].

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