1. Tip60 HAT Action Mediates Environmental Enrichment Induced Cognitive Restoration
- Author
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Priyalakshmi Panikker, Sahira Iqbal, Felice Elefant, and Song-Jun Xu
- Subjects
0301 basic medicine ,Transcription, Genetic ,lcsh:Medicine ,Biochemistry ,Histones ,Amyloid beta-Protein Precursor ,0302 clinical medicine ,Cognition ,Animal Cells ,Medicine and Health Sciences ,Drosophila Proteins ,Post-Translational Modification ,lcsh:Science ,Promoter Regions, Genetic ,Histone Acetyltransferases ,Regulation of gene expression ,Genetics ,Neurons ,Cognitive Impairment ,Multidisciplinary ,Cognitive Neurology ,Chromosome Biology ,Pyramidal Cells ,Chromatin Modification ,Chemical Reactions ,Acetylation ,Histone Modification ,Neurodegenerative Diseases ,Chromatin ,Cell biology ,Protein Transport ,Chemistry ,Histone ,Neurology ,Physical Sciences ,Drosophila ,Epigenetics ,Alzheimer's disease ,Cellular Types ,Research Article ,Cognitive Neuroscience ,Histone Acetylation ,DNA transcription ,Biology ,Environment ,03 medical and health sciences ,Open Reading Frames ,Mediator ,Alzheimer Disease ,Mental Health and Psychiatry ,medicine ,Animals ,Mushroom Bodies ,Cell Nucleus ,Environmental enrichment ,lcsh:R ,fungi ,Biology and Life Sciences ,Proteins ,Cell Biology ,medicine.disease ,Rats ,030104 developmental biology ,Gene Expression Regulation ,Cellular Neuroscience ,Synapses ,biology.protein ,Cognitive Science ,lcsh:Q ,Dementia ,Gene expression ,030217 neurology & neurosurgery ,Biomarkers ,Neuroscience - 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.
- Published
- 2016