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Tip60 HAT Action Mediates Environmental Enrichment Induced Cognitive Restoration
Journal article   Open access   Peer reviewed

Tip60 HAT Action Mediates Environmental Enrichment Induced Cognitive Restoration

Songjun Xu, Priyalakshmi Panikker, Sahira Iqbal and Felice Elefant
PloS one, v 11(7), pp e0159623-e0159623
2016
DOI: https://doi.org/10.1371/journal.pone.0159623
PMID: 27454757
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1371/journal.pone.0159623View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Acetylation Alzheimer Disease - genetics Alzheimer Disease - metabolism Alzheimer Disease - pathology Amyloid beta-Protein Precursor - metabolism Animals Biomarkers Cell Nucleus - metabolism Cognition Drosophila Drosophila Proteins - genetics Drosophila Proteins - metabolism Environment Gene Expression Regulation Histone Acetyltransferases - genetics Histone Acetyltransferases - metabolism Histones - metabolism Mushroom Bodies - physiology Open Reading Frames Promoter Regions, Genetic Protein Transport Pyramidal Cells - metabolism Rats Synapses - metabolism Transcription, Genetic
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.

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Web of Science research areas
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