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Glutathione hypothesis of schizophrenia

Collaborators at the Centre for Psychiatric Neuroscience (CPN) at Cery have proposed the new hypothesis that schizophrenia involves a deficit in the antioxidant glutathione, and have linked this with the more classical role of dopamine - see CNP-schizophrenia. In collaboration with the CPN, DNF researchers have tested this hypothesis in rodents with altered dopamine metabolism, and have found specific structural defects in this animal model involving the pyramidal neurons and the inhibitory interneurons of the anterior cingulate cortex, thus underlying a developmentally-regulated misconnectivity in cortical limbic structures - see Hornung.

The above hypothesis concerning glutathione implies that protein oxidation should be changed in schizophrenia. Therefore, DNF (and CPN) researchers are using a proteomic analysis of fibroblasts cultured from biopsy tissue of schizophrenic patients or healthy controls to discover whether certain proteins from the fibroblasts of schizophrenics are more readily oxidized in response to oxidative stress - see Riederer.

Phencyclidine model of schizophrenia

Whereas the glutathione hypothesis mentioned above is concerned with the fundamental causes of subtle brain damage underlying schizophrenia, we also need to understand the more immediate causes and consequences of changed brain activity in this disease. It has long been known that phencyclidine ("PCP" - also called "angel dust" by drug abusers) causes schizophrenic symptoms. At the molecular level, phencyclidine is an antagonist of the NMDA type of glutamate receptor, and it leads to reduced electrical activity and impaired synaptic plasticity in several brain regions, including notably the frontal lobe. Researchers of the DNF and the CNP are studying rodents treated for 7-14 days with phencyclidine, analysing its effects at all levels from neuronal cell biology to behaviour - see Volterra.

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