DeltaFosB: a molecular switch for long-term adaptation in the brain.

DeltaFosB is a unique transcription factor that plays an essential role in long-term adaptive changes in the brain associated with diverse conditions, such as drug addiction, Parkinson's disease, depression, and antidepressant treatment. It is induced in brain, in a region- and cell-type-specific manner by many types of chronic perturbations. Once induced, it persists for long periods of time due to its unusual stability. The transcriptional effects of DeltaFosB are complex, because the protein can function as both a transcriptional activator and repressor. Progress has been made in identifying specific target genes for DeltaFosB and in relating some of these genes to DeltaFosB's cellular and behavioral actions. Future studies will help us to better understand the biochemical basis of DeltaFosB's unique stability, as well as the precise molecular pathways through which this transcription factor produces its complex effects on neuronal plasticity and complex behavior.

[1]  G. Bing,et al.  Long‐Term Expression of Fos‐Related Antigen and Transient Expression of ΔFosB Associated with Seizures in the Rat Hippocampus and Striatum , 1997, Journal of neurochemistry.

[2]  M. Cenci Transcription factors involved in the pathogenesis of L-DOPA-induced dyskinesia in a rat model of Parkinson's disease , 2002, Amino Acids.

[3]  M. Greenberg,et al.  Essential Role of the fosB Gene in Molecular, Cellular, and Behavioral Actions of Chronic Electroconvulsive Seizures , 1998, The Journal of Neuroscience.

[4]  F. J. White,et al.  Repeated administration of cocaine or amphetamine alters neuronal responses to glutamate in the mesoaccumbens dopamine system. , 1995, The Journal of pharmacology and experimental therapeutics.

[5]  Rachael L Neve,et al.  CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[6]  H. Wiśniewski,et al.  The spatio-temporal pattern of Wallerian degeneration in mammalian peripheral nerves. , 1973, Brain research.

[7]  C. Chiamulera,et al.  Common Neural Substrates for the Addictive Properties of Nicotine and Cocaine , 1997, Science.

[8]  David W. Self,et al.  Induction of a long-lasting AP-1 complex composed of altered Fos-like proteins in brain by chronic cocaine and other chronic treatments , 1994, Neuron.

[9]  M. Ehrlich,et al.  Periadolescent Mice Show Enhanced ΔFosB Upregulation in Response to Cocaine and Amphetamine , 2002, The Journal of Neuroscience.

[10]  M. Andersson,et al.  Time course of striatal DeltaFosB-like immunoreactivity and prodynorphin mRNA levels after discontinuation of chronic dopaminomimetic treatment. , 2003, The European journal of neuroscience.

[11]  N. Hiroi,et al.  Region‐specific induction of ΔFosB by repeated administration of typical versus atypical antipsychotic drugs , 1999, Synapse.

[12]  N. Hiroi,et al.  Regulation of cocaine reward by CREB. , 1998, Science.

[13]  Ann M Graybiel,et al.  Network-Level Changes in Expression of Inducible Fos–Jun Proteins in the Striatum during Chronic Cocaine Treatment and Withdrawal , 1996, Neuron.

[14]  A. Graybiel,et al.  Atypical and typical neuroleptic treatments induce distinct programs of transcription factor expression in the striatum , 1996, The Journal of comparative neurology.

[15]  I. Verma,et al.  An alternative spliced form of FosB is a negative regulator of transcriptional activation and transformation by Fos proteins. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[16]  E. Nestler,et al.  Induction of chronic Fos-related antigens in rat brain by chronic morphine administration. , 1996, Molecular pharmacology.

[17]  M. Greenberg,et al.  FosB mutant mice: loss of chronic cocaine induction of Fos-related proteins and heightened sensitivity to cocaine's psychomotor and rewarding effects. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[18]  C. Colby,et al.  Inducible, brain region-specific expression of a dominant negative mutant of c-Jun in transgenic mice decreases sensitivity to cocaine , 2003, Brain Research.

[19]  M. Angela Cenci,et al.  cAMP Response Element-Binding Protein Is Required for Dopamine-Dependent Gene Expression in the Intact But Not the Dopamine-Denervated Striatum , 2001, The Journal of Neuroscience.

[20]  J. Cadet,et al.  Methamphetamine-induced increase in striatal NF-kappaB DNA-binding activity is attenuated in superoxide dismutase transgenic mice. , 1998, Brain research. Molecular brain research.

[21]  M. Kelz,et al.  Pharmacological studies of the regulation of chronic FOS-related antigen induction by cocaine in the striatum and nucleus accumbens. , 1995, The Journal of pharmacology and experimental therapeutics.

[22]  P. Greengard,et al.  Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5 , 2001, Nature.

[23]  E. Nestler,et al.  Elevated levels of ΔFosB and RGS9 in striatum in Parkinson’s disease , 2001, Biological Psychiatry.

[24]  J. Morgan,et al.  MPTP-Parkinsonism is accompanied by persistent expression of a delta-FosB-like protein in dopaminergic pathways. , 1998, Brain research. Molecular brain research.

[25]  M. Kelz,et al.  Chronic Fos-Related Antigens: Stable Variants of ΔFosB Induced in Brain by Chronic Treatments , 1997, The Journal of Neuroscience.

[26]  E. Nestler,et al.  Striatal Cell Type-Specific Overexpression of ΔFosB Enhances Incentive for Cocaine , 2003, The Journal of Neuroscience.

[27]  J. Morgan,et al.  Absence of a Persistently Elevated 37 kDa Fos-Related Antigen and AP-1-Like DNA-Binding Activity in the Brains of Kainic Acid-TreatedfosB Null Mice , 1997, The Journal of Neuroscience.

[28]  Michael E Greenberg,et al.  A Defect in Nurturing in Mice Lacking the Immediate Early Gene fosB , 1996, Cell.

[29]  E. Nestler,et al.  Induction of nuclear factor‐κB in nucleus accumbens by chronic cocaine administration , 2001, Journal of neurochemistry.

[30]  B Kolb,et al.  Persistent Structural Modifications in Nucleus Accumbens and Prefrontal Cortex Neurons Produced by Previous Experience with Amphetamine , 1997, The Journal of Neuroscience.

[31]  Mark J. Thomas,et al.  Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine , 2001, Nature Neuroscience.

[32]  E. Nestler,et al.  Chronic electroconvulsive seizure (ECS) treatment results in expression of a long-lasting AP-1 complex in brain with altered composition and characteristics , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[33]  M. Barrot,et al.  Induction of ΔFosB in Reward-Related Brain Structures after Chronic Stress , 2004, The Journal of Neuroscience.

[34]  P. Greengard,et al.  Neuronal and behavioural abnormalities in striatal function in DARPP‐32‐mutant mice , 1999, The European journal of neuroscience.

[35]  T. Curran,et al.  Immediate-early genes: ten years on , 1995, Trends in Neurosciences.

[36]  M. Kelz,et al.  Transgenic animals with inducible, targeted gene expression in brain. , 1998, Molecular pharmacology.

[37]  M. Kelz,et al.  Regulation of delta FosB and FosB-like proteins by electroconvulsive seizure and cocaine treatments. , 1995, Molecular pharmacology.

[38]  D. Surmeier,et al.  Expression of the transcription factor ΔFosB in the brain controls sensitivity to cocaine , 1999, Nature.

[39]  R. Baler,et al.  Differential regulation of fos family genes in the ventrolateral and dorsomedial subdivisions of the rat suprachiasmatic nucleus , 2000, Neuroscience.

[40]  M. Andersson,et al.  Striatal fosB Expression Is Causally Linked with l -DOPA-Induced Abnormal Involuntary Movements and the Associated Upregulation of Striatal Prodynorphin mRNA in a Rat Model of Parkinson's Disease , 1999, Neurobiology of Disease.

[41]  Y. Nakabeppu,et al.  A naturally occurring truncated form of FosB that inhibits Fos/Jun transcriptional activity , 1991, Cell.

[42]  M. Barrot,et al.  ΔFosB: A sustained molecular switch for addiction , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[43]  Eric J. Nestler,et al.  ΔFosB Regulates Wheel Running , 2002, The Journal of Neuroscience.

[44]  C. McClung,et al.  Regulation of gene expression and cocaine reward by CREB and ΔFosB , 2003, Nature Neuroscience.

[45]  E. Nestler,et al.  Downregulation of the CCAAT-Enhancer Binding Protein β in ΔFosB Transgenic Mice and by Electroconvulsive Seizures , 2004, Neuropsychopharmacology.

[46]  T. Noguchi,et al.  Both products of the fosB gene, FosB and its short form, FosB/SF, are transcriptional activators in fibroblasts. , 1991, Molecular and cellular biology.

[47]  P. Greengard,et al.  Cocaine-induced proliferation of dendritic spines in nucleus accumbens is dependent on the activity of cyclin-dependent kinase-5 , 2003, Neuroscience.

[48]  M. Kelz,et al.  Induction of Cyclin-Dependent Kinase 5 in the Hippocampus by Chronic Electroconvulsive Seizures: Role of ΔFosB , 2000, The Journal of Neuroscience.

[49]  M. Kelz,et al.  &Dgr;FosB: a molecular switch underlying long-term neural plasticity , 2000, Current opinion in neurology.

[50]  S. Hyman,et al.  Regulation of immediate early gene expression and AP-1 binding in the rat nucleus accumbens by chronic cocaine. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[51]  E. Nestler,et al.  Chronic Alterations in Dopaminergic Neurotransmission Produce a Persistent Elevation of ΔFosB‐like Protein(s) in both the Rodent and Primate Striatum , 1996, The European journal of neuroscience.