GABAergic neuronal subtypes in the human frontal cortex--development and deficits in schizophrenia.
Recent studies have provided evidence for a deficit of GABA-containing interneurons in the frontal cortex in schizophrenia. That this deficit might be brought about during early foetal or neonatal life is a hypothesis consistent with the substantial indications for a neurodevelopmental aetiology of the disease. GABAergic neurons can be defined by the presence of one of three types of calcium binding proteins, which are thought to have neuroprotective properties. We have undertaken an investigation into the postnatal ontology of these neuronal subtypes and find that calretinin expression is relatively constant and present from before birth, calbindin expression is also present early but redistributes in the cortex over the first months of life, while parvalbumin-immunoreactivity is not observed until between 3 and 6 months of age. Investigation of frontal cortical tissue taken post mortem from a series of schizophrenic patients and matched control subjects revealed that parvalbumin-, but not calretinin-immunoreactive cells are significantly diminished in schizophrenia. These observations support the hypothesis that GABAergic deficits in schizophrenia may stem from toxic events occurring during cortical development which selectively target immature neurons before protection by parvalbumin is conferred.
Reynolds
G P
GP
Department of Biomedical Science, The University of Sheffield, Western Bank, S10 2TN, Sheffield, UK. g.p.reynolds@sheffield.ac.uk
Beasley
C L
CL
D000368:Aged; D000375:Aging / Q000502:physiology; D064032:Calbindin 2; D064026:Calbindins; D005260:Female; D005625:Frontal Lobe / Q000002:abnormalities* / Q000254:growth & development / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009421:Nervous System Malformations / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010320:Parvalbumins / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D012559:Schizophrenia / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
C576764:CALB2 protein, human; D064032:Calbindin 2; D064026:Calbindins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D005680:gamma-Aminobutyric Acid