of associations with substance abuse and Parkinson’s disease. Am J Med Genet B Neuropsychiatr Genet 134:93–103. Liu QR, Lu L, Zhu XG, Gong JP, Shaham Y, Uhl GR. 2006. Rodent BDNF genes, novel promoters, novel splice variants, regulation by co- caine. Brain Res 1067:1–12. Lunyak VV, Burgess R, Prefontaine GG, Nelson C, Sze SH, Chenoweth J, Schwartz P, Pevzner PA, Glass C, Mandel G, Rosenfeld MG. 2002. Corepressor-dependent silencing of chromosomal regions encoding neu- ronal genes. Science 298:1747–1752. Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y, Fan G, Sun YE. 2003. DNA methylation-related chromatin remodeling in activity- dependent BDNF gene regulation. Science 302:890–893. Mellstrom B, Torres B, Link WA, Naranjo JR. 2004. The BDNF gene: exemplifying complexity in Ca2+-dependent gene expression. Crit Rev Neurobiol 16:43–49. Metsis M, Timmusk T, Arenas E, Persson H. 1993. Differential usage of multiple brain-derived neurotrophic factor promoters in the rat brain fol- lowing neuronal activation. Proc Natl Acad Sci U S A 90:8802–8806. Mogi M, Togari A, Kondo T, Mizuno Y, Komure O, Kuno S, Ichinose H, Nagatsu T. 1999. Brain-derived growth factor and nerve growth fac- tor concentrations are decreased in the substantia nigra in Parkinson’s disease. Neurosci Lett 270. Mowla SJ, Farhadi HF, Pareek S, Atwal JK, Morris SJ, Seidah NG, Mur- phy RA. 2001. Biosynthesis and post-translational processing of the pre- cursor to brain-derived neurotrophic factor. J Biol Chem 276:12660– 12666. Murer MG, Yan Q, Raisman-Vozari R. 2001. Brain-derived neurotrophic factor in the control human brain and in Alzheimer’s disease and Parkin- son’s disease. Prog Neurobiol 63:71–124. Palm K, Belluardo N, Metsis M, Timmusk T. 1998. Neuronal expression of zinc ﬁnger transcription factor REST/NRSF/XBR gene. J Neurosci 18:1280–1296. Parain K, Murer MG, Yan Q, Faucheux B, Agid Y, Hirsch E, Raisman- Vozari R. 1999. Reduced expression of brain-derived neurotrophic fac- tor protein in Parkinson’s disease substantia nigra. Neuroreport 10:557– 561. Phillips HS, Hains JM, Armanini M, Laramee GR, Johnson SA, Winslow JW. 1991. BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer’s disease. Neuron 7:695–702. Russo-Neustadt AA, Chen MJ. 2005. Brain-derived neurotrophic factor and antidepressant activity. Curr Pharm Des 11:1495–1510. Sathanoori M, Dias BG, Nair AR, Banerjee SB, Tole S, Vaidya VA. 2004. Differential regulation of multiple brain-derived neurotrophic factor transcripts in the postnatal and adult rat hippocampus during develop- ment, in response to kainate administration. Brain Res Mol Brain Res 130:170–177. Schoenherr CJ, Anderson DJ. 1995. The neuron-restrictive silencer factor (NRSF): a coordinate repressor of multiple neuron-speciﬁc genes. Sci- ence 267:1360–1363. Shieh PB, Ghosh A. 1999. Molecular mechanisms underlying activity- dependent regulation of BDNF expression. J Neurobiol 41:127–134. Shieh PB, Hu SC, Bobb K, Timmusk T, Ghosh A. 1998. Identiﬁcation of a signaling pathway involved in calcium regulation of BDNF expression. Neuron 20:727–740. Tabuchi A, Sakaya H, Kisukeda T, Fushiki H, Tsuda M. 2002. Involve- ment of an upstream stimulatory factor as well as cAMP-responsive ele- ment-binding protein in the activation of brain-derived neurotrophic factor gene promoter I. J Biol Chem 277:35920–35931. Tao X, Finkbeiner S, Arnold DB, Shaywitz AJ, Greenberg ME. 1998. Ca2+ inﬂux regulates BDNF transcription by a CREB family transcrip- tion factor-dependent mechanism. Neuron 20:709–726. Journal of Neuroscience Research DOI 10.1002/jnr BDNF Gene Structure in Rodents 535 Tao X, West AE, Chen WG, Corfas G, Greenberg ME. 2002. A calcium- responsive transcription factor, CaRF, that regulates neuronal activity- dependent expression of BDNF. Neuron 33:383–395. Teng HK, Teng KK, Lee R, Wright S, Tevar S, Almeida RD, Kermani P, Torkin R, Chen ZY, Lee FS, et al. 2005. ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin. J Neurosci 25:5455–5463. Teng KK, Hempstead BL. 2004. Neurotrophins and their receptors: sig- naling trios in complex biological systems. Cell Mol Life Sci 61:35–48. Timmusk T, Palm K, Metsis M, Reintam T, Paalme V, Saarma M, Persson H. 1993. Multiple promoters direct tissue-speciﬁc expression of the rat BDNF gene. Neuron 10:475–489. Timmusk T, Lendahl U, Funakoshi H, Arenas E, Persson H, Metsis M. 1995. Identiﬁcation of brain-derived neurotrophic factor promoter regions mediating tissue-speciﬁc, axotomy-, and neuronal activity- induced expression in transgenic mice. J Cell Biol 128:185–199. Timmusk T, Palm K, Lendahl U, Metsis M. 1999. Brain-derived neuro- trophic factor expression in vivo is under the control of neuron-restric- tive silencer element. J Biol Chem 274:1078–1084. Tsankova NM, Kumar A, Nestler EJ. 2004. Histone modiﬁcations at gene promoter regions in rat hippocampus after acute and chronic electrocon- vulsive seizures. J Neurosci 24:5603–5610. Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ. 2006. Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci 9:519–525. Tyler WJ, Alonso M, Bramham CR, Pozzo-Miller L. 2002. From acquisi- tion to consolidation: on the role of brain-derived neurotrophic factor signaling in hippocampal-dependent learning. Learn Mem 9:224–237. West AE, Chen WG, Dalva MB, Dolmetsch RE, Kornhauser JM, Shaywitz AJ, Takasu MA, Tao X, Greenberg ME. 2001. Calcium regu- lation of neuronal gene expression. Proc Natl Acad Sci U S A 98:11024– 11031. Woo NH, Teng HK, Siao CJ, Chiaruttini C, Pang PT, Milner TA, Hempstead BL, Lu B. 2005. Activation of p75NTR by proBDNF facili- tates hippocampal long-term depression. Nat Neurosci 8:1069–1077. Wood IC, Belyaev ND, Bruce AW, Jones C, Mistry M, Roopra A, Buck- ley NJ. 2003. Interaction of the repressor element 1-silencing transcrip- tion factor (REST) with target genes. J Mol Biol 334:863–874. Yamada K, Mizuno M, Nabeshima T. 2002. Role for brain-derived neu- rotrophic factor in learning and memory. Life Sci 70:735–744. Yan Q, Rosenfeld RD, Matheson CR, Hawkins N, Lopez OT, Bennett L, Welcher AA. 1997. Expression of brain-derived neurotrophic factor pro- tein in the adult rat central nervous system. Neuroscience 78:431–448. Zafra F, Hengerer B, Leibrock J, Thoenen H, Lindholm D. 1990. Activity dependent regulation of BDNF and NGF mRNAs in the rat hippocam- pus is mediated by non-NMDA glutamate receptors. EMBO J 9:3545– 3550. Zafra F, Castren E, Thoenen H, Lindholm D. 1991. Interplay between glutamate and gamma-aminobutyric acid transmitter systems in the physi- ological regulation of brain-derived neurotrophic factor and nerve growth factor synthesis in hippocampal neurons. Proc Natl Acad Sci U S A 88: 10037–10041. Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, MacDonald ME, Friedlander RM, Silani V, Hayden MR, et al. 2001. Loss of huntingtin-mediated BDNF gene transcription in Huntington’s disease. Science 293:493–498. Zuccato C, Tartari M, Crotti A, Goffredo D, Valenza M, Conti L, Catau- della T, Leavitt BR, Hayden MR, Timmusk T, et al. 2003. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE- controlled neuronal genes. Nat Genet 35:76–83.