Apigenin attenuates isoflurane-induced cognitive dysfunction via epigenetic regulation and neuroinflammation in aged rats. (November 2017)

• Record Type: Journal Article
• Authors: Chen, Lin; Xie, Wenji; Xie, Wenqin; Zhuang, Weiqiang; Jiang, Changcheng; Liu, Naizhen
• Is Part Of: Archives of gerontology and geriatrics. Volume 73(2017)
• Page Start: 29
• Page End: 36
• Publication Date: 2017-11
• Subjects: POCD post operational cognitive dysfunction -- HDAC1 histone deacetylase 1 -- CBP CREB binding protein; Post operational cognitive dysfunction -- Anesthesia -- Isoflurane -- Apigenin -- Aged; Aging -- Periodicals; Geriatrics -- Periodicals; Gerontology -- Periodicals; Electronic journals; 305.26
• DOI: 10.1016/j.archger.2017.07.004
• Languages: English
• ISSNs: 0167-4943

Abstract

Highlights: Isoflurane exposure induces memory impairment. Apigenin recovers cognitive function. Apigenin restores histone acetylation and suppress neuroinflammation. Abstract: Purpose of the research: Post operational cognitive dysfunction (POCD) occurs in patients after anesthesia and surgery. Abnormal histone acetylation and neuroinflammation are key factors in the pathogenesis of cognitive impairment. Apigenin not only has an anti-inflammatory activity but also modifies histone acetylation. We aimed to investigate whether apigenin can attenuate isoflurane exposure-induced cognitive decline by regulating histone acetylation and inflammatory signaling. Materials and methods: Spatial learning and memory were assessed by Morris water maze test. Levels of histone acetylation, BDNF and downstream signaling, and inflammatory components were analyzed. Principal results: Isoflurane exposure in aged rats lead to impaired spatial learning and memory. These rats exhibited dysregulated histone H3K9 and H4K12 acetylation, which was accompanied by reduced BDNF expression and suppressed BDNF downstream signaling pathway. Apigenin restored histone acetylation and BDNF signaling. Apigenin also suppressed isoflurane exposure induced upregulation of proinflammatory cytokines and NFκB signaling pathway. Major conclusions: Memory impairment induced by isoflurane exposure is associated with dysregulated histone acetylation in the hippocampus, which affects BDNF expression and hence BDNF downstream signaling pathway. Apigenin recovers cognitive function by restoring histone acetylation and suppressing neuroinflammation.