TY - JOUR
T1 - Analysis of complex brain disorders with gene expression microarrays
T2 - Schizophrenia as a disease of the synapse
AU - Mirnics, Károly
AU - Middleton, Frank A.
AU - Lewis, David A.
AU - Levitt, Pat
PY - 2001/8/1
Y1 - 2001/8/1
N2 - The level of cellular and molecular complexity of the nervous system creates unique problems for the neuroscientist in the design and implementation of functional genomic studies. Microarray technologies can be powerful, with limitations, when applied to the analysis of human brain disorders. Recently, using cDNA microarrays, altered gene expression patterns between subjects with schizophrenia and controls were shown. Functional data mining led to two novel discoveries: a consistent decrease in the group of transcripts encoding proteins that regulate presynaptic function; and the most changed gene, which has never been previously associated with schizophrenia, regulator of G-protein signaling 4. From these and other findings, a hypothesis has been formulated to suggest that schizophrenia is a disease of the synapse. In the context of a neurodevelopmental model, it is proposed that impaired mechanics of synaptic transmission in specific neural circuits during childhood and adolescence ultimately results in altered synapse formation or pruning, or both, which manifest in the clinical onset of the disease.
AB - The level of cellular and molecular complexity of the nervous system creates unique problems for the neuroscientist in the design and implementation of functional genomic studies. Microarray technologies can be powerful, with limitations, when applied to the analysis of human brain disorders. Recently, using cDNA microarrays, altered gene expression patterns between subjects with schizophrenia and controls were shown. Functional data mining led to two novel discoveries: a consistent decrease in the group of transcripts encoding proteins that regulate presynaptic function; and the most changed gene, which has never been previously associated with schizophrenia, regulator of G-protein signaling 4. From these and other findings, a hypothesis has been formulated to suggest that schizophrenia is a disease of the synapse. In the context of a neurodevelopmental model, it is proposed that impaired mechanics of synaptic transmission in specific neural circuits during childhood and adolescence ultimately results in altered synapse formation or pruning, or both, which manifest in the clinical onset of the disease.
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U2 - 10.1016/S0166-2236(00)01862-2
DO - 10.1016/S0166-2236(00)01862-2
M3 - Review article
C2 - 11476888
AN - SCOPUS:0035426751
VL - 24
SP - 479
EP - 486
JO - Trends in Neurosciences
JF - Trends in Neurosciences
SN - 0378-5912
IS - 8
ER -