title: Genetic deletion of Gadd45b, a regulator of active DNA demethylation, enhances long-term memory and synaptic plasticity.
abstract: Dynamic epigenetic mechanisms including histone and DNA modifications regulate animal behavior and memory. While numerous enzymes regulating these mechanisms have been linked to memory formation, the regulation of active DNA demethylation (i.e., cytosine-5 demethylation) has only recently been investigated. New discoveries aim toward the Growth arrest and DNA damage-inducible 45 (Gadd45) family, particularly Gadd45b, in activity-dependent demethylation in the adult CNS. This study found memory-associated expression of gadd45b in the hippocampus and characterized the behavioral phenotype of gadd45b(-/-) mice. Results indicate normal baseline behaviors and initial learning but enhanced persisting memory in mutants in tasks of motor performance, aversive conditioning and spatial navigation. Furthermore, we showed facilitation of hippocampal long-term potentiation in mutants. These results implicate Gadd45b as a learning-induced gene and a regulator of memory formation and are consistent with its potential role in active DNA demethylation in memory.
authors.affiliation: Department of Neurobiology and Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Faraz A
authors.initials: FA
authors.lastname: Sultan
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tront
authors.forename: Dan A
authors.initials: DA
authors.lastname: Liebermann
authors.forename: J David
authors.initials: JD
authors.lastname: Sweatt
mesh_terms: D000679:Amygdala / Q000166:cytology / Q000502:physiology*; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics* / Q000378:metabolism; D001522:Behavior, Animal / Q000502:physiology; D002478:Cells, Cultured; D019175:DNA Methylation / Q000235:genetics*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D017774:Long-Term Potentiation / Q000235:genetics*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D057567:Memory, Long-Term / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000502:physiology; D013037:Spatial Behavior / Q000502:physiology; D013569:Synapses / Q000235:genetics* / Q000378:metabolism; D000097642:GADD45 Proteins
chemical_list: D000943:Antigens, Differentiation; C490125:Gadd45b protein, mouse; D000097642:GADD45 Proteins