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Temporal changes in mouse brain fatty acid amide hydrolase activity.

S T Glaser1, M Kaczocha

  • 1Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY 11794-5230, USA. sherrye.glaser@stonybrook.edu

Neuroscience
|June 27, 2009
PubMed
Summary

This study reveals daily fluctuations in brain Fatty Acid Amide Hydrolase (FAAH) activity. Understanding these temporal changes is crucial for developing effective FAAH-targeted therapies for pain and anxiety.

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Imaging of the brain cannabinoid system.

Handbook of experimental pharmacology·2006
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The cellular uptake of anandamide is coupled to its breakdown by fatty-acid amide hydrolase.

The Journal of biological chemistry·2000
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Area of Science:

  • Neuroscience
  • Pharmacology
  • Biochemistry

Background:

  • Fatty acid amide hydrolase (FAAH) regulates endocannabinoid levels, including anandamide.
  • FAAH inhibition offers therapeutic potential for analgesia and anxiolysis without motor impairment.
  • Endogenous fluctuations in brain FAAH activity remain largely uncharacterized.

Purpose of the Study:

  • To comprehensively investigate temporal fluctuations in mouse brain FAAH activity.
  • To determine if FAAH activity varies between the light (noon) and dark (midnight) cycles.
  • To assess regional differences in these temporal FAAH activity changes.

Main Methods:

  • Collected regional mouse brain homogenates at the midpoint of light and dark cycles.
  • Utilized immunoblots and in vitro activity assays to measure FAAH activity.

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  • Employed a novel ex vivo autoradiography technique to analyze FAAH activity in 11 brain regions.

    • Main Results:

    • In vitro assays showed a 10% reduction in cerebellar FAAH activity at midnight.
    • Immunoblots found no significant regional activity changes between time points.
    • Ex vivo autoradiography revealed significant FAAH activity reductions in the cerebellum and periaqueductal gray at midnight.

    Conclusions:

    • Mouse brain FAAH activity exhibits significant temporal fluctuations, particularly in specific regions like the cerebellum and periaqueductal gray.
    • These findings highlight the importance of considering circadian rhythms when developing FAAH-targeting therapeutics.
    • Temporal variations in FAAH activity must be accounted for to optimize therapeutic strategies.