Recovery of learning and memory is associated with chromatin remodelling.
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.
Fischer
Andre
A
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
Sananbenesi
Farahnaz
F
Wang
Xinyu
X
Dobbin
Matthew
M
Tsai
Li-Huei
LH
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
D002087:Butyrates; D002843:Chromatin; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases