title: Decreased chloride channel expression in the dorsolateral prefrontal cortex in schizophrenia.
abstract: Alterations in GABAergic neurotransmission are implicated in several psychiatric illnesses, including schizophrenia. The Na-K-Cl and K-Cl cotransporters regulate intracellular chloride levels. Abnormalities in cotransporter expression levels could shift the chloride electrochemical gradient and impair GABAergic transmission. In this study, we performed Western blot analysis to investigate whether the Na-K-Cl and K-Cl cotransporter protein is abnormally expressed in the dorsal lateral prefrontal cortex and the anterior cingulate cortex in patients with schizophrenia versus a control group. We found decreased K-Cl cotransporter protein expression in the dorsal lateral prefrontal cortex, but not the anterior cingulate cortex, in subjects with schizophrenia, supporting the hypothesis of region level abnormal GABAergic function in the pathophysiology of schizophrenia. Subjects with schizophrenia off antipsychotic medication at the time of death had decreased K-Cl cotransporter protein expression compared to both normal controls and subjects with schizophrenia on antipsychotics. Our results provide evidence for KCC2 protein abnormalities in schizophrenia and suggest that antipsychotic medications might reverse deficits of this protein in the illness.
authors.affiliation: University of Cincinnati College of Medicine, Neuroscience Graduate Program, Cincinnati, Ohio, United States of America; Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Courtney R
authors.initials: CR
authors.lastname: Sullivan
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Funk
authors.affiliation: Department of Nephrology, University of Alabama Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Dan
authors.initials: D
authors.lastname: Shan
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, United States of America; James J Peters Veterans Affairs Medical Center, New York, New York, United States of America.
authors.forename: Vahram
authors.initials: V
authors.lastname: Haroutunian
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Robert E
authors.initials: RE
authors.lastname: McCullumsmith
mesh_terms: D018118:Chloride Channels / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D017397:Prefrontal Cortex / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*
chemical_list: D018118:Chloride Channels
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