Glutathione deficit during development induces anomalies in the rat anterior cingulate GABAergic neurons: Relevance to schizophrenia.
A series of studies in schizophrenic patients report a decrease of glutathione (GSH) in prefrontal cortex (PFC) and cerebrospinal fluid, a decrease in mRNA levels for two GSH synthesizing enzymes and a deficit in parvalbumin (PV) expression in a subclass of GABA neurons in PFC. GSH is an important redox regulator, and its deficit could be responsible for cortical anomalies, particularly in regions rich in dopamine innervation. We tested in an animal model if redox imbalance (GSH deficit and excess extracellular dopamine) during postnatal development would affect PV-expressing neurons. Three populations of interneurons immunolabeled for calcium-binding proteins were analyzed quantitatively in 16-day-old rat brain sections. Treated rats showed specific reduction in parvalbumin immunoreactivity in the anterior cingulate cortex, but not for calbindin and calretinin. These results provide experimental evidence for the critical role of redox regulation in cortical development and validate this animal model used in schizophrenia research.
Center for Research in Psychiatric Neuroscience, Department of Adult Psychiatry-CHUV, University of Lausanne, 1008-Prilly, Switzerland. Jan-Harry.Cabungcal@hospvd.ch
Jan-Harry
JH
Cabungcal
Dominique
D
Nicolas
Rudolf
R
Kraftsik
Michel
M
Cuénod
Kim Q
KQ
Do
Jean-Pierre
JP
Hornung
D000818:Animals; D001923:Brain Chemistry; D064032:Calbindin 2; D064026:Calbindins; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D045604:Extracellular Fluid / Q000737:chemistry; D005978:Glutathione / Q000172:deficiency*; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism; D017397:Prefrontal Cortex / Q000254:growth & development* / Q000378:metabolism*; D051381:Rats; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C576512:Calb2 protein, rat; D064032:Calbindin 2; D064026:Calbindins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D005680:gamma-Aminobutyric Acid; D005978:Glutathione; D004298:Dopamine