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Recovery of learning and memory is associated with chromatin remodelling

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TLDR
It is shown that environmental enrichment reinstated learning behaviour and re-established access to long-term memories after significant brain atrophy and neuronal loss had already occurred, and suggests that inhibition of histone deacetylases might be a suitable therapeutic avenue for neurodegenerative diseases associated with learning and memory impairment.
Abstract
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-term memories after significant brain atrophy and neuronal loss had already occurred Environmental enrichment correlated with chromatin modifications (increased histone-tail acetylation) Moreover, increased histone acetylation by inhibitors of histone deacetylases induced sprouting of dendrites, an increased number of synapses, and reinstated learning behaviour and access to long-term memories These data suggest that inhibition of histone deacetylases might be a suitable therapeutic avenue for neurodegenerative diseases associated with learning and memory impairment, and raises the possibility of recovery of long-term memories in patients with dementia

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Citations
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Journal ArticleDOI

The many roles of histone deacetylases in development and physiology: Implications for disease and therapy

TL;DR: In this article, the expression of many HDAC isoforms in eukaryotic cells raises questions about their possible specificity or redundancy, and whether they control global or specific programs of gene expression.
Book

Preventing Mental, Emotional, and Behavioral Disorders Among Young People: Progress and Possibilities

TL;DR: Mental, emotional, and behavioral (MEB) disorders—which include depression, conduct disorder, and substance abuse—affect large numbers of young people.
Journal ArticleDOI

Alzheimer mechanisms and therapeutic strategies.

TL;DR: Investigative and drug development efforts should be diversified to fully address the multifactoriality of Alzheimer's disease.
References
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Journal ArticleDOI

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TL;DR: The results of these studies point to the importance of the hippocampal complex for normal memory function in patients who had undergone similar, but less radical, bilateral medial temporallobe resections, and as a warning to others of the risk to memory involved in bilateral surgical lesions of the hippocampusal region.
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Modality-specific retrograde amnesia of fear.

TL;DR: The results indicate that fear memory is not a single process and that the hippocampus may have a time-limited role in associative fear memories evoked by polymodal (contextual) but not unimodal (tone) sensory stimuli.
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Neural consequences of environmental enrichment.

TL;DR: This article focuses on the neuronal changes that occur in response to complex stimulation by an enriched environment and emphasizes the behavioural and neurobiological consequences of specific elements of enrichment, especially exercise and learning.
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Tau Suppression in a Neurodegenerative Mouse Model Improves Memory Function

TL;DR: NFTs are not sufficient to cause cognitive decline or neuronal death in this model of tauopathy, and after the suppression of transgenic tau, memory function recovered, and neuron numbers stabilized, but to the authors' surprise, NFTs continued to accumulate.
Journal ArticleDOI

Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action

TL;DR: 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.
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