The Impact of Oxidative Stress on GAD67 Levels and Parvalbumin-Positive Neurons

  • Jessica Deslauriers
  • Sylvain Grignon
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)


GAD67, product of the GAD1 gene, and GAD65, product of GAD2, are critically involved in the control of GABA synthesis in the central nervous system. Since the initial report of decreased transcription levels of GAD67 in the prefrontal cortex of patients with schizophrenia, the finding of decreased GAD transcript and protein levels has been very generally replicated, making it the most consistent neurochemical abnormality in schizophrenia and to some extent in bipolar affective disorder. The concomitant decrease of the calcium-binding protein parvalbumin has been reported with similar regularity, and these neurochemical perturbations relate to the dysfunction of a network of cortical or hippocampal GABAergic interneurons, notably basket and chandelier cells. Among the potential mechanisms leading to this decrease, the hypofunction of the NMDA receptor has attracted the most attention and has been shown recently to involve increased oxidative stress, originating from NADPH oxidase activation. Lastly, a large preclinical and cognitive literature suggests that a dysfunctional frontal GABAergic network is associated to abnormal electroencephalographic spectra, which are thought to underlie higher cognitive functions and are known to be disturbed in schizophrenia.

Therefore, the investigation of GAD abnormalities in schizophrenia provides a coherent framework to account for the impact of oxidative stress on pathological phenomena ranging from cellular to cognitive and clinical aspects.


Glutamic Acid Decarboxylase Axon Initial Segment NMDAR Antagonist Gaba Neurotransmission GAD67 Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Brodmann area




Glutamic acid decarboxylase




Methylazoxymethanol acetate


NADPH oxidase

poly IC

Polyinosinic: polycytidylic acid




Reverse transcriptase-quantitative polymerase chain reaction


Toll-like receptor 3


Toll-like receptor 4


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© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Département de PsychiatrieCentre Hospitalier Universitaire de SherbrookeSherbrookeCanada
  2. 2.Departments of Psychiatry and Physiology& BiophysicsUniversity of SherbrookeSherbrookeCanada

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