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Accession IconGSE5080

Harmane Alters the Expression of a Subset of Genes with Diverse Functions in Primary Human Astrocytes

Organism Icon Homo sapiens
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Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

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Essential tremor (ET) is the most common movement disorder in adults, but little is known about the molecular mechanisms underlying ET pathogenesis. Harmane is a member of a group of tremorogenic chemicals. In humans, increased blood harmane concentration is associated with increased risk of ET. Astrocytes are essential for brain function, and astrocyte dysfuctions are associated with many neurodegenerative diseases. Therefore, we identified the molecular targets of harmane in primary human astrocytes by using microarray gene expression profiling and computational analysis algorithms. We found that harmane altered the expression of a limited number of genes encoding diverse functions. Notably, the transcript levels of two GABA receptors and a GABA transporter were altered by harmane, consistent with previous evidence suggesting that the GABAergic neurotransmission system may be disrupted in ET. Also, we found that the transcript levels of two prominent proinflammatory enzymes, the inducible nitric oxide synthase NOS2A and the cyclooxygenase COX2, and 10 other targets of the proinflammatory IFN-gamma signaling pathway were up-regulated by harmane. These results together raise the possibility that perturbation of the expression of functions involved in neurotransmission and inflammatory activation of astrocytes might be important mechanisms underlying the neurotoxicity of harmane and ET pathogenesis.
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