title: Recovery of learning and memory is associated with chromatin remodelling.
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.
authors.affiliation: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139, USA. andre.fischer@mpi-mail.mpg.de
authors.forename: Andre
authors.initials: A
authors.lastname: Fischer
authors.forename: Farahnaz
authors.initials: F
authors.lastname: Sananbenesi
authors.forename: Xinyu
authors.initials: X
authors.lastname: Wang
authors.forename: Matthew
authors.initials: M
authors.lastname: Dobbin
authors.forename: Li-Huei
authors.initials: LH
authors.lastname: Tsai
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002087:Butyrates / Q000494:pharmacology; D002843:Chromatin / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D003704:Dementia / Q000503:physiopathology; D004777:Environment; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009473:Neuronal Plasticity / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
chemical_list: D002087:Butyrates; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases