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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
30
pubmed:dateCreated
2011-7-28
pubmed:abstractText
GABA signaling molecules are critical for both human brain development and the pathophysiology of schizophrenia. We examined the expression of transcripts derived from three genes related to GABA signaling [GAD1 (GAD67 and GAD25), SLC12A2 (NKCC1), and SLC12A5 (KCC2)] in the prefrontal cortex (PFC) and hippocampal formation of a large cohort of nonpsychiatric control human brains (n = 240) across the lifespan (from fetal week 14 to 80 years) and in patients with schizophrenia (n = 30-31), using quantitative RT-PCR. We also examined whether a schizophrenia risk-associated promoter SNP in GAD1 (rs3749034) is related to expression of these transcripts. Our studies revealed that development and maturation of both the PFC and hippocampal formation are characterized by progressive switches in expression from GAD25 to GAD67 and from NKCC1 to KCC2. Previous studies have demonstrated that the former leads to GABA synthesis, and the latter leads to switching from excitatory to inhibitory neurotransmission. In the hippocampal formation, GAD25/GAD67 and NKCC1/KCC2 ratios are increased in patients with schizophrenia, reflecting a potentially immature GABA physiology. Remarkably, GAD25/GAD67 and NKCC1/KCC2 expression ratios are associated with rs3749034 genotype, with risk alleles again predicting a relatively less mature pattern. These findings suggest that abnormalities in GABA signaling critical to brain development contribute to genetic risk for schizophrenia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
27
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11088-95
pubmed:meshHeading
pubmed-meshheading:21795557-Adolescent, pubmed-meshheading:21795557-Adult, pubmed-meshheading:21795557-Aged, pubmed-meshheading:21795557-Aged, 80 and over, pubmed-meshheading:21795557-Animals, pubmed-meshheading:21795557-Antipsychotic Agents, pubmed-meshheading:21795557-Cerebral Cortex, pubmed-meshheading:21795557-Child, pubmed-meshheading:21795557-Child, Preschool, pubmed-meshheading:21795557-Cohort Studies, pubmed-meshheading:21795557-Female, pubmed-meshheading:21795557-Fetus, pubmed-meshheading:21795557-Gene Expression Regulation, Developmental, pubmed-meshheading:21795557-Genotype, pubmed-meshheading:21795557-Glutamate Decarboxylase, pubmed-meshheading:21795557-Hippocampus, pubmed-meshheading:21795557-Humans, pubmed-meshheading:21795557-Infant, pubmed-meshheading:21795557-Infant, Newborn, pubmed-meshheading:21795557-Male, pubmed-meshheading:21795557-Middle Aged, pubmed-meshheading:21795557-RNA, Messenger, pubmed-meshheading:21795557-Rats, pubmed-meshheading:21795557-Rats, Sprague-Dawley, pubmed-meshheading:21795557-Schizophrenia, pubmed-meshheading:21795557-Signal Transduction, pubmed-meshheading:21795557-Sodium-Potassium-Chloride Symporters, pubmed-meshheading:21795557-Symporters, pubmed-meshheading:21795557-gamma-Aminobutyric Acid
pubmed:year
2011
pubmed:articleTitle
Expression of GABA signaling molecules KCC2, NKCC1, and GAD1 in cortical development and schizophrenia.
pubmed:affiliation
Section on Neuropathology, Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA. hydet@mail.nih.gov
pubmed:publicationType
Journal Article