PT  - JOURNAL ARTICLE
AU  - Fabien Dutheil
AU  - Sandrine Dauchy
AU  - Monique Diry
AU  - Véronique Sazdovitch
AU  - Olivier Cloarec
AU  - Lucille Mellottée
AU  - Ivan Bièche
AU  - Magnus Ingelman-Sundberg
AU  - Jean-Pierre Flinois
AU  - Isabelle de Waziers
AU  - Philippe Beaune
AU  - Xavier Declèves
AU  - Charles Duyckaerts
AU  - Marie-Anne Loriot
TI  - Xenobiotic-Metabolizing Enzymes and Transporters in the Normal Human Brain: Regional and Cellular Mapping as a Basis for Putative Roles in Cerebral Function
AID  - 10.1124/dmd.109.027011
DP  - 2009 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 1528--1538
VI  - 37
IP  - 7
4099  - http://dmd.aspetjournals.org/content/37/7/1528.short
4100  - http://dmd.aspetjournals.org/content/37/7/1528.full
SO  - Drug Metab Dispos2009 Jul 01; 37
AB  - Cytochrome P450 (P450) enzymes and ATP-binding cassette (ABC) transporters modulate the transport and metabolism of both endogenous and exogenous substrates and could play crucial roles in the human brain. In this study, we report the transcript expression profile of seven ABC transporters (ABCB1, ABCC1–C5, and ABCG2), 24 P450s (CYP1, CYP2, and CYP3 families and CYP46A1), and 14 related transcription factors [aryl hydrocarbon receptor, nuclear receptor (NR)1I2/pregnane X receptor, NR1I3/constitutive androstane receptor and NR1C/peroxisome proliferator-activated receptor, NR1H/liver X receptor, NR2B/retinoid X receptor, and NR3A/estrogen receptor subfamilies] in the whole brain, the dura mater, and 17 different encephalic areas. In addition, Western blotting and immunohistochemistry analysis were used to characterize the distribution of the P450s at the cellular and subcellular levels in some brain regions. Our results show the presence of a large variety of xenobiotic transporters and metabolizing enzymes in human brain and show for the first time their apparent selective distribution in different cerebral regions. The most abundant transporters were ABCC5 and ABCG2, which, interestingly, had a higher mRNA expression in the brain compared with that found in the liver. CYP46A1, CYP2J2, CYP2U1, CYP1B1, CYP2E1, and CYP2D6 represented more than 90% of the total P450 and showed selective distribution in different brain regions. Their presence in both microsomal and mitochondrial fractions was shown both in neuronal and glial cells in several brain areas. Thus, our study shows key enzymes of cholesterol and fatty acid metabolism to be present in the human brain and provides novel information of importance for elucidation of enzymes responsible for normal and pathological processes in the human brain.