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Decreased chloride channel expression in the dorsolateral prefrontal cortex in schizophrenia.

Sullivan CR, Funk AJ, Shan D, Haroutunian V, McCullumsmith RE - PLoS ONE (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

NKCC1 and KCC2 Expression in DLPFC.Expression of Na-K-Cl cotransporter (NKCC1) (A, D) and K-Cl cotransporter (KCC2) (B, E) protein in the DLPFC in control subjects (CTL) and subjects with schizophrenia (SCZ) (A, B) and in subjects with schizophrenia on and off medication for at least 6 weeks (D, E). Expression of KCC2 protein in the ACC in control subjects (CTL) and subjects with schizophrenia (SCZ) (C) and in subjects with schizophrenia on and off medication for at least 6 weeks (F). *P<0.05 **P<0.05 compared to KCC2 expression in the DLPFC of control subjects. Data are shown as mean ± SEM.
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pone.0123158.g002: NKCC1 and KCC2 Expression in DLPFC.Expression of Na-K-Cl cotransporter (NKCC1) (A, D) and K-Cl cotransporter (KCC2) (B, E) protein in the DLPFC in control subjects (CTL) and subjects with schizophrenia (SCZ) (A, B) and in subjects with schizophrenia on and off medication for at least 6 weeks (D, E). Expression of KCC2 protein in the ACC in control subjects (CTL) and subjects with schizophrenia (SCZ) (C) and in subjects with schizophrenia on and off medication for at least 6 weeks (F). *P<0.05 **P<0.05 compared to KCC2 expression in the DLPFC of control subjects. Data are shown as mean ± SEM.

Mentions: No significant associations were found between pH, post-mortem interval (PMI) or age and any of our dependent measures. In subjects with schizophrenia, we found a 22% decrease in KCC2 protein expression in the DLPFC [F(1,58) = 2.140, p<0.05]. We did not detect changes in NKCC1 protein levels in this region (Fig 2A and 2B). To determine if changes in KCC2 expression were region-specific, we measured KCC2 protein levels in the ACC. We did not any detect changes in KCC2 expression in the ACC (Fig 2C).


Decreased chloride channel expression in the dorsolateral prefrontal cortex in schizophrenia.

Sullivan CR, Funk AJ, Shan D, Haroutunian V, McCullumsmith RE - PLoS ONE (2015)

NKCC1 and KCC2 Expression in DLPFC.Expression of Na-K-Cl cotransporter (NKCC1) (A, D) and K-Cl cotransporter (KCC2) (B, E) protein in the DLPFC in control subjects (CTL) and subjects with schizophrenia (SCZ) (A, B) and in subjects with schizophrenia on and off medication for at least 6 weeks (D, E). Expression of KCC2 protein in the ACC in control subjects (CTL) and subjects with schizophrenia (SCZ) (C) and in subjects with schizophrenia on and off medication for at least 6 weeks (F). *P<0.05 **P<0.05 compared to KCC2 expression in the DLPFC of control subjects. Data are shown as mean ± SEM.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4380350&req=5

pone.0123158.g002: NKCC1 and KCC2 Expression in DLPFC.Expression of Na-K-Cl cotransporter (NKCC1) (A, D) and K-Cl cotransporter (KCC2) (B, E) protein in the DLPFC in control subjects (CTL) and subjects with schizophrenia (SCZ) (A, B) and in subjects with schizophrenia on and off medication for at least 6 weeks (D, E). Expression of KCC2 protein in the ACC in control subjects (CTL) and subjects with schizophrenia (SCZ) (C) and in subjects with schizophrenia on and off medication for at least 6 weeks (F). *P<0.05 **P<0.05 compared to KCC2 expression in the DLPFC of control subjects. Data are shown as mean ± SEM.
Mentions: No significant associations were found between pH, post-mortem interval (PMI) or age and any of our dependent measures. In subjects with schizophrenia, we found a 22% decrease in KCC2 protein expression in the DLPFC [F(1,58) = 2.140, p<0.05]. We did not detect changes in NKCC1 protein levels in this region (Fig 2A and 2B). To determine if changes in KCC2 expression were region-specific, we measured KCC2 protein levels in the ACC. We did not any detect changes in KCC2 expression in the ACC (Fig 2C).

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus