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Related Experiment Videos

Decrease in GABA synthesis rate in rat cortex following GABA-transaminase inhibition correlates with the decrease in

G F Mason1, D L Martin, S B Martin

  • 1Department of Psychiatry, Magnetic Resonance Center for Research in Metabolism and Physiology, Yale University School of Medicine, New Haven, CT 06520, USA. graeme.mason@yale.edu

Brain Research
|October 2, 2001
PubMed
Summary
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Vigabatrin treatment significantly reduces brain gamma-aminobutyric acid (GABA) synthesis flux, primarily by decreasing GAD(67) levels. This highlights GAD(67)

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pharmacology

Background:

  • Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain.
  • Glutamic acid decarboxylase (GAD) exists as two isoforms, GAD(65) and GAD(67), both involved in GABA synthesis.
  • The quantitative contribution of each GAD isoform to GABA synthesis flux remains unclear.

Purpose of the Study:

  • To quantitatively compare GABA synthesis flux (V(GAD)) between control and vigabatrin-treated rats.
  • To determine the roles of GAD(65) and GAD(67) in regulating V(GAD) under basal and inhibited conditions.

Main Methods:

  • Utilized [1-13C]glucose infusion and ex vivo/in vivo 13C NMR spectroscopy.
  • Employed an extended model of glutamate-glutamine cycling including a GABAergic compartment.

Related Experiment Videos

  • Measured total GAD activity and GAD isoform composition via enzymatic assay and quantitative immunoblotting.

    • Main Results:

    • Vigabatrin treatment significantly decreased V(GAD) by 67-70% compared to controls.
    • This reduction was associated with decreased total GAD activity and a selective 44% decrease in GAD(67) protein.
    • GAD(65) protein levels remained unchanged, suggesting GAD(67) accounts for the majority of basal GABA synthesis.

    Conclusions:

    • GAD(67) accounts for 56-85% of basal cortical GABA synthesis flux.
    • Vigabatrin treatment significantly inhibits GABA synthesis, with GAD(67) reduction playing a major role.
    • Further investigation is needed to elucidate the precise mechanisms of GAD inhibition by vigabatrin.