Microarray analysis of thyroid hormone-induced changes in mRNA expression in the adult rat brain.

To determine which genes in the adult rat brain are regulated by thyroid hormone (TH), we used microarrays to examine the effect of hyperthyroidism on neuron-specific gene expression. Four-month-old male Fisher 344 rats were rendered hyperthyroid by intraperitoneal injection of 3,5,3'-L-triiodothyronine (T3, 15 microg/100 g body weight) for 10 consecutive days. To minimize interindividual variability, pooled cerebral tissue RNA from four-control and five-hyperthyroid rats was hybridized in duplicates to the Affymetrix (Santa Clara, CA) U34N rat neurobiology microarray, which contains probes for 1224 neural-specific genes. Changes in gene expression were considered significant only if they were observed in both pair-wise comparisons as well as by Northern blot analysis. Hyperthyroidism was associated with modest changes in the expression of only 11 genes. The expression of the phosphodiesterase Enpp2, myelin oligodendrocyte glycoprotein (Mog), microtubule-associated protein 2 (MAP2), growth hormone (GH), Ca(2+)/calmodulin-dependent protein kinase beta-subunit (Camk2b), neuron-specific protein PEP-19 (Pcp4), a sodium-dependent neurotransmitter, and the myelin-associated glycoprotein (S-MAG) was significantly increased. Three genes were suppressed by hyperthyroidism, including the activity and neurotransmitter-induced early genes-1 and -7 (ANIA-1 and ANIA-7) and the guanine nucleotide-binding protein one (Gnb1). The present study underscores the paucity of TH responsive genes in adult cerebral tissue.