Transitions in the transcriptome of the serotonergic and dopaminergic systems in the human brain during adolescence.
Adolescence is a period of profound neurophysiological, behavioral, cognitive and psychological changes, but not much is known about the underlying molecular neural mechanisms. The aim of this study was to systematically analyze expression levels of the genes forming serotonergic and dopaminergic synapses during adolescence. We analyzed the mRNA expression profiles of genes that code for all components of serotonergic and dopaminergic synapses, in 16 brain areas from human and non-human primates from public domain databases, to detect genes whose expression changes during adolescence. Two serotonin receptors, HTR1E and HTR1B had expression levels that exhibit a sharp transition in the prefrontal cortex in adolescence, but we found no similar transition in the dopaminergic system. A similar but smoother rise in expression levels is observed in HTR4 and HTR5A, and in HTR1E and HTR1B in three other expression datasets published. An earlier rise is observed in HTR1A, and a smooth and significant rise with age is observed in the expression of HTR1E in microarray measurements in macaque monkeys. The expression of HTR1E and HTR1B is correlated across subjects within each age group, suggesting that they are controlled by common mechanisms. These results point to HTR1E and HTR1B as major candidate genes involved in adolescence maturation processes, and to their operation through common control mechanisms. The maturation profiles may also involve several other 5-HT receptors, including the genes HTR5A, HTR4 and HTR1A.
Geha Mental Health Center, Petah Tiqva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Gal
G
Shoval
Gonda Brain Research Center, Bar-Ilan University, Ramat Gan 52900, Israel.
Ossnat
O
Bar-Shira
Geha Mental Health Center, Petah Tiqva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University, New York, NY, USA.
Gil
G
Zalsman
Division of Molecular Imaging and Neuropathology, Department of Psychiatry, Columbia University, New York, NY, USA.
J
J
John Mann
Gonda Brain Research Center, Bar-Ilan University, Ramat Gan 52900, Israel. Electronic address: Gal.Chechik@biu.ac.il.
Gal
G
Chechik
D000293:Adolescent; D000328:Adult; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D008253:Macaca mulatta; D011954:Receptors, Dopamine / Q000235:genetics* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000235:genetics* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome; D055815:Young Adult
D050483:Dopamine Plasma Membrane Transport Proteins; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D004298:Dopamine
5-HT(1B); 5-HT(1E); Adolescence; Dopamine; Serotonin