Yuta Ishizuka    Department   Kawasaki Medical School  Kawasaki Medical School, Department of Pathophysiology and Metabolism,    Position   Assistant Professor
Article types	原著
Language	English
Peer review	Peer reviewed
Title	Histone deacetylase mediates the decrease in drebrin cluster density induced by amyloid beta oligomers.
Journal	Formal name：Neurochemistry international Abbreviation：Neurochem Int ISSN code：18729754/01970186
Domestic / Foregin	Foregin
Publisher	ScienceDirect
Volume, Issue, Page	76,pp.114-21
Author and coauthor	Yuta Ishizuka, Hideo Shimizu, Eiko Takagi, Mai Kato, Hirotaka Yamagata, Masahiko Mikuni, Tomoaki Shirao
Authorship	Lead author
Publication date	2014/10
Summary	Dendritic spine defects are found in a number of cognitive disorders, including Alzheimer's disease (AD). Amyloid beta (Aβ) toxicity is mediated not only by the fibrillar form of the protein, but also by the soluble oligomers (Aβ-derived diffusible ligands, ADDLs). Drebrin is an actin-binding protein that is located at mature dendritic spines. Because drebrin expression is decreased in AD brains and in cultured neurons exposed to Aβ, it is thought that drebrin is closely associated with cognitive functions. Recent studies show that histone deacetylase (HDAC) activity is elevated in the AD mouse model, and that memory impairments in these animals can be ameliorated by HDAC inhibitors. In addition, spine loss and memory impairment in HDAC2 over-expressing mice are ameliorated by chronic HDAC inhibitor treatment. Therefore, we hypothesized that the regulation of histone acetylation/deacetylation is critical to synaptic functioning. In this study, we examined the relationship between HDAC activity and synaptic defects induced by ADDLs using an HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA). We show that ADDLs reduce the cluster density of drebrin along dendrites without reducing drebrin expression. SAHA markedly increased the acetylation of histone proteins, and it simultaneously attenuated the ADDL-induced decrease in drebrin cluster density. In comparison, SAHA treatment did not affect the density of drebrin clusters or dendritic protrusions in control neurons. Therefore, SAHA likely inhibits ADDL-induced drebrin loss from dendritic spines by stabilizing drebrin in these structures, rather than by increasing drebrin clusters or dendritic protrusions. Taken together, our findings suggest that HDAC is involved in ADDL-induced synaptic defects, and that the regulation of histone acetylation plays an important role in modulating actin cytoskeletal dynamics in dendritic spines under cellular stress conditions, such as ADDL exposure.
DOI	10.1016/j.neuint.2014.07.005
PMID	25058791