Functional analysis of gene expression in risperidone treated cells provide new insights in molecular mechanism and new candidate genes for pharmacogenetic studies
作者： Sergi Mas , Patricia Gassó , Miquel Bernardo , Amalia Lafuente
DOI: 10.1016/J.EURONEURO.2012.04.016
关键词: Synaptic plasticity 、 Neurogenesis 、 Neuroscience 、 Neurotransmission 、 Risperidone 、 Biology 、 Dopamine 、 Candidate gene 、 Neurotransmitter 、 5-HT receptor
摘要: Abstract Risperidone is a potent antagonist of both dopamine and serotonin receptors. However, little known about the underlying molecular mechanism by which risperidone acts. Although number genetic variants have been observed to correlate with treatment response there are no definitive predictors response. We performed genome-wide gene expression analysis (Human Genome U219 Array Plate) human neuroblastoma cell line (SK-N-SH) exposed identify mechanisms involved in cellular thus candidate genes for pharmacogenetic studies. Our results revealed that associated range changes, time (6–48 h) dose related (0.1–10 μM). found functional clusters these changes correspond Gene Ontology categories neural development functions, synaptic structure functions. also identified Canonical Pathways categories: neurogenesis axon guidance; vesicle; neurotransmitter signaling (dopamine, glutamate). Finally, we studies main secondary effects: motor disorders, cardiovascular disorders metabolic disorders. suggest affects neurotransmission cells, agreement “initiation adaptation” model explain action psychotropic drugs.
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