Proceedings of the National Academy of Sciences · 2001 · 1.2K citations · 23 references
Life SciencesNeurosciencePsychiatryGene ExpressionMolecular NeuroscienceNeuropsychiatryMolecular NeurogeneticsNeural DevelopmentNeurodevelopmental GeneticsNeuropsychiatric GeneticsPsychiatric GeneticsSchizophrenia Spectrum DisordersDifferential Transcript ExpressionMicroarray AnalysisMyelin-associated Gene ExpressionMyelination DisruptionMyelination Gene ExpressionNeuronal ConnectivityOligodendrocyte FunctionOligodendrocyte Gene Expression
Neuropathological and brain imaging studies suggest schizophrenia may stem from neurodevelopmental defects, with cytoarchitectural evidence of disrupted neuronal connectivity in the dorsolateral prefrontal cortex, yet the underlying molecular mechanisms remain unclear. The study aimed to identify molecular substrates linked to schizophrenia by profiling gene expression in postmortem dorsolateral prefrontal cortex tissue. DNA microarray analysis was employed to assay gene expression levels in postmortem dorsolateral prefrontal cortex samples from schizophrenic and control patients. Differentially expressed genes were enriched for synaptic plasticity, neuronal development, neurotransmission, and signal transduction pathways, with the most striking change being in myelination‑related genes, suggesting oligodendrocyte dysfunction in schizophrenia.
Neuropathological and brain imaging studies suggest that schizophrenia may result from neurodevelopmental defects. Cytoarchitectural studies indicate cellular abnormalities suggestive of a disruption in neuronal connectivity in schizophrenia, particularly in the dorsolateral prefrontal cortex. Yet, the molecular mechanisms underlying these findings remain unclear. To identify molecular substrates associated with schizophrenia, DNA microarray analysis was used to assay gene expression levels in postmortem dorsolateral prefrontal cortex of schizophrenic and control patients. Genes determined to have altered expression levels in schizophrenics relative to controls are involved in a number of biological processes, including synaptic plasticity, neuronal development, neurotransmission, and signal transduction. Most notable was the differential expression of myelination-related genes suggesting a disruption in oligodendrocyte function in schizophrenia.
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Expression monitoring by hybridization to high-density oligonucleotide arrays
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