title: Tip60 HAT Action Mediates Environmental Enrichment Induced Cognitive Restoration.
abstract: Environmental enrichment (EE) conditions have beneficial effects for reinstating cognitive ability in neuropathological disorders like Alzheimer's disease (AD). While EE benefits involve epigenetic gene control mechanisms that comprise histone acetylation, the histone acetyltransferases (HATs) involved remain largely unknown. Here, we examine a role for Tip60 HAT action in mediating activity- dependent beneficial neuroadaptations to EE using the Drosophila CNS mushroom body (MB) as a well-characterized cognition model. We show that flies raised under EE conditions display enhanced MB axonal outgrowth, synaptic marker protein production, histone acetylation induction and transcriptional activation of cognition linked genes when compared to their genotypically identical siblings raised under isolated conditions. Further, these beneficial changes are impaired in both Tip60 HAT mutant flies and APP neurodegenerative flies. While EE conditions provide some beneficial neuroadaptive changes in the APP neurodegenerative fly MB, such positive changes are significantly enhanced by increasing MB Tip60 HAT levels. Our results implicate Tip60 as a critical mediator of EE-induced benefits, and provide broad insights into synergistic behavioral and epigenetic based therapeutic approaches for treatment of cognitive disorder.
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, United States of America.
authors.forename: Songjun
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, United States of America.
authors.forename: Priyalakshmi
authors.initials: P
authors.lastname: Panikker
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, United States of America.
authors.forename: Sahira
authors.initials: S
authors.lastname: Iqbal
authors.affiliation: Department of Biology, Drexel University, Philadelphia, PA, United States of America.
authors.forename: Felice
authors.initials: F
authors.lastname: Elefant
mesh_terms: D000107:Acetylation; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D002467:Cell Nucleus / Q000378:metabolism; D003071:Cognition; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004777:Environment; D005786:Gene Expression Regulation; D051548:Histone Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D024521:Mushroom Bodies / Q000502:physiology*; D016366:Open Reading Frames; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D029721:Drosophila Proteins; D006657:Histones; D051548:Histone Acetyltransferases; C511056:Tip60 protein, Drosophila