Recovery of learning and memory is associated with chromatin remodelling

  title={Recovery of learning and memory is associated with chromatin remodelling},
  author={Andr{\'e} Fischer and Farahnaz Sananbenesi and Xinyu Wang and Matthew M. Dobbin and Li-Huei Tsai},
Neurodegenerative diseases of the central nervous system are often associated with impaired learning and memory, eventually leading to dementia. An important aspect in pre-clinical research is the exploration of strategies to re-establish learning ability and access to long-term memories. By using a mouse model that allows temporally and spatially restricted induction of neuronal loss, we show here that environmental enrichment reinstated learning behaviour and re-established access to long… 
Inhibition of Histone Deacetylase Reinstates Hippocampus-Dependent Long-Term Synaptic Plasticity and Associative Memory in Sleep-Deprived Mice.
It is demonstrated that modifying epigenetic mechanisms via SAHA can prevent or reverse impairments in long-term plasticity and memory that result from sleep loss, and could be a potential therapeutic agent in improving SD-related memory deficits.
Environmental Enrichment: Aging and Memory
  • T. Patel
  • Biology
    The Yale journal of biology and medicine
  • 2012
Through understanding the mechanisms by which environmental enrichment and histone acetylation interact in the brain and affect learning and memory, novel applications can be developed for therapeutic interventions to neurodegenerative diseases and aging.
Epigenetics: Reclaiming lost memories
  • K. Whalley
  • Biology, Psychology
    Nature Reviews Neuroscience
  • 2007
The results not only suggest that memory impairments might be overcome by strategies that can induce neuronal plasticity, but also indicate histone deacetylases as suitable protein targets for drug therapies.
Phenylbutyrate rescues dendritic spine loss associated with memory deficits in a mouse model of Alzheimer disease
The data suggest that the beneficial effects of PBA in memory are mediated both via its chemical chaperone‐like activity and via the transcriptional activation of a cluster of proteins required for the induction of synaptic plasticity and structural remodeling.
An epigenetic blockade of cognitive functions in the neurodegenerating brain
Reversing the build-up of histone deacetylase 2 by short-hairpin-RNA-mediated knockdown unlocks the repression of genes, reinstates structural and synaptic plasticity, and abolishes neurodegeneration-associated memory impairments.
Environmental Enrichment Reverses Histone Methylation Changes in the Aged Hippocampus and Restores Age-Related Memory Deficits
Results suggest that histone lysine methylation levels are abnormally regulated in the aged hippocampus and identify hist one lysines methylation as a transcriptional mechanism by which EE may serve to restore memory formation with aging.
HDAC inhibitor-dependent transcriptome and memory reinstatement in cognitive decline models.
It is determined that aging and amyloid pathology are associated with inflammation and impaired synaptic function in the hippocampal CA1 region as the result of epigenetic-dependent alterations in gene expression, and histone deacetylase inhibitors should be further explored as a cost-effective therapeutic strategy against age-associated cognitive decline.
Behavioural neuroscience: Down memory lane
In mice, two treatments — environmental enrichment and a chemical that regulates gene expression — boost new memory formation and restore the recall of old memories that seemed to have been lost, and this memory boost occurs, despite severe brain atrophy, in the p25 mice.
Altered Histone Acetylation Is Associated with Age-Dependent Memory Impairment in Mice
It is shown that memory disturbances in the aging brain of the mouse are associated with altered hippocampal chromatin plasticity, and data suggest that deregulated H4K12 acetylation may represent an early biomarker of an impaired genome-environment interaction in the Aging mouse brain.


Regulation of Histone Acetylation during Memory Formation in the Hippocampus*
Results indicate that histone-associated heterochromatin undergoes changes in structure during the formation of long term memory, which enhances a cellular process thought to underlie longterm memory formation, hippocampal long term potentiation, and memory formation itself.
Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action
An important role for histone remodeling in the pathophysiology and treatment of depression is underscored and the therapeutic potential for hist one methylation and deacetylation inhibitors in depression is highlighted.
Enriched environments, experience-dependent plasticity and disorders of the nervous system
Findings on the environmental modulators of pathogenesis and gene–environment interactions in CNS disorders, and their therapeutic implications, are reviewed.
Neural Network Modeling of Memory Deterioration in Alzheimer's Disease
A neural network model is used to investigate how the interplay between synaptic deletion and compensation determines the pattern of memory deterioration, a clinical hallmark of AD, and shows that the deterioration of memory retrieval due to synaptic deletion can be much delayed.
Handling and environmental enrichment do not rescue learning and memory impairments in αCamKIIT286A mutant mice
The lack of autophosphorylation of the α‐isoform of the Ca2+/calmodulin‐dependent kinase II prevents enrichment‐induced rescues of strategy learning and memory impairments and it is established that there are enrichment mechanisms that are independent of this autoph phosphorylation.
Neuronal-Based Synaptic Compensation: A Computational Study in Alzheimer's Disease
It is shown that following synaptic deletion, synaptic compensation can be carried out efficiently by a local, dynamic mechanism, where each neuron maintains the profile of its incoming post-synaptic current.