title: Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, attenuates postoperative cognitive dysfunction in aging mice.
abstract: Postoperative cognitive dysfunction (POCD) is a recognized clinical entity characterized with cognitive deficits after anesthesia and surgery, especially in aged patients. Previous studies have shown that histone acetylation plays a key role in hippocampal synaptic plasticity and memory formation. However, its role in POCD remains to be determined. Here, we show that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, attenuates POCD in aging Mice. After exposed to the laparotomy, a surgical procedure involving an incision into abdominal walls to examine the abdominal organs, 16- but not 3-month old male C57BL/6 mice developed obvious cognitive impairments in the test of long-term contextual fear conditioning. Intracerebroventricular (i.c.v.) injection of SAHA at the dose of (20 μg/2 μl) 3 h before and daily after the laparotomy restored the laparotomy-induced reduction of hippocampal acetyl-H3 and acetyl-H4 levels and significantly attenuated the hippocampus-dependent long-term memory (LTM) impairments in 16-month old mice. SAHA also reduced the expression of cleaved caspase-3, inducible nitric oxide synthase (iNOS) and N-methyl-D-aspartate (NMDA) receptor-calcium/calmodulin dependent kinase II (CaMKII) pathway, and increased the expression of brain-derived neurotrophic factor (BDNF), synapsin 1, and postsynaptic density 95 (PSD95). Taken together, our data suggest that the decrease of histone acetylation contributes to POCD and may serve as a target to improve the neurological outcome of POCD.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: Wen-Xue
authors.initials: WX
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: He-Liang
authors.initials: HL
authors.lastname: Sun
authors.affiliation: Institute of Aging Research, School of Medicine, Hangzhou Normal University Hangzhou, China.
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Chang
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China ; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College Xuzhou, China ; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology Xuzhou, China.
authors.forename: Jiao-Jiao
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China.
authors.forename: Mu-Huo
authors.initials: MH
authors.lastname: Ji
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University Nanjing, China ; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College Xuzhou, China ; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology Xuzhou, China.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Yang
authors.affiliation: Institute of Aging Research, School of Medicine, Hangzhou Normal University Hangzhou, China.
authors.forename: Chen-Zhuo
authors.initials: CZ
authors.lastname: Feng
keywords: aging; histone acetylation; neuroapoptosis; postoperative cognitive dysfunction; synaptic plasticity