Research Report Rodent BDNF genes, novel promoters, novel splice variants, and regulation by cocaine ☆ Qing-Rong Liu a , Lin Lu b , Xu-Guang Zhu a , Jian-Ping Gong a , Yavin Shaham b , George R. Uhl a, ⁎ a Molecular Neurobiology Branch, National Institute on Drug Abuse-Intramural Research Program (NIDA-IRP), NIH, Department of Health and Human Services (DHHS), Box 5180, Baltimore, MD 21224, USA b Behaviour Neuroscience Branch, National Institute on Drug Abuse-Intramural Research Program (NIDA-IRP), NIH, Department of Health and Human Services (DHHS), Baltimore, MD 21224, USA ARTICLE INFO ABSTRACT Article history: Accepted 2 October 2005 Available online 22 December 2005 Results from studies using molecular and genetic methods in humans and rodents suggest that brain-derived neurotrophic factor (BDNF) is involved in the behavioral effects of abused drugs, making understanding of its genomic structure and regulation of substantial interest. Recently, we have reported that the human BDNF gene contains seven upstream exons that can each be spliced independently to the major BDNF coding exon to form diverse bipartite BDNF transcripts. We also identified a novel “BDNFOS” gene that is transcribed to produce alternatively spliced natural antisense transcripts (NATs); its fifth exon overlaps with the protein coding exon VIII of human BDNF. To better understand BDNF's genomic structure and differential regulation, we now describe the rodent BDNF gene and transcripts. This gene includes six bipartite transcripts that are generated by six independently transcribed exons, each of which is spliced to a major coding exon and a tripartite transcript that is composed of two upstream exons and one coding exon. In addition, we found no evidence for antisense, opposite strand BDNFOS gene transcripts in mice or rats. The BDNF rodent splice variants display specific patterns of differential expression in different brain regions and peripheral tissues. Acute cocaine administration increased striatal expression of a specific BDNF4 splice variant by up to 5-fold. Interestingly, however, neither experimenter- nor self-administered chronic cocaine administration enhanced striatal BDNF expression. These data suggest a role of specific BDNF promoter regions and regulatory sequences in stimulant-induced alterations in BDNF expression, and in the alterations that changed BDNF expression is likely to confer in the brain. Published by Elsevier B.V. Theme: Cellular and molecular biology Topic: Gene structure and function: general Keywords: Neurotrophin Gene regulation Addiction Dopamine Cocaine BRAIN RESEARCH 1067 (2006) 1 – 12 ☆ NCBI GenBank accession numbers. Mouse BDNF gene sequence: AY057907. Mouse BDNF cDNA sequences: mBDNF1, AY057908; mBDNF2A, AY057909; mBDNF2B, AY057910; mBDNF2C, AY057911; mBDNF3, AY057912; mBDNF4, AY057913; mBDNF5, AY057914; mBDNF6A, AY231131; and mBDNF6B, AY231132. Rat cDNA sequences: rBDNF3, AY559248; rBDNF6A, AY559249; rBDNF6B, AY559250. ⁎ Corresponding author. Fax: +1 410 550 1535. E-mail address: guhl@intra.nida.nih.gov (G.R. Uhl). 0006-8993/$ – see front matter. Published by Elsevier B.V. doi:10.1016/j.brainres.2005.10.004 available at www.sciencedirect.com www.elsevier.com/locate/brainres