1. Epigenetic modulation of the MAPK pathway prevents isoflurane-induced neuronal apoptosis and cognitive decline in aged rats
- Author
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Hui‑Hui Cheng, Yao Lv, Qing-Tao Meng, Yun‑Ping Cheng, Sheng‑Lan Mei, Zhongyuan Xia, Lei Huang, and Hai‑Bin Fang
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,Cancer Research ,medicine.medical_specialty ,hippocampus ,p38 mitogen-activated protein kinases ,Morris water navigation task ,Biology ,cognitive ,03 medical and health sciences ,isoflurane ,0302 clinical medicine ,Immunology and Microbiology (miscellaneous) ,Internal medicine ,medicine ,histone-deacetylase ,Cognitive decline ,epigenetics ,apoptosis ,General Medicine ,Articles ,MAPK ,030104 developmental biology ,Endocrinology ,Isoflurane ,Apoptosis ,030220 oncology & carcinogenesis ,Anesthetic ,Histone deacetylase ,medicine.drug - Abstract
Isoflurane is a broadly used inhalation anesthetic that causes cognitive impairment in rodent models as well as humans. Although previous studies suggested an association between isoflurane exposure and neuro-inflammation, apoptosis and mitochondrial dysfunction, the pathogenesis of isoflurane-induced cognitive decline remains elusive. In the present study, 22-month-old male Sprague-Dawley male rats (n=96) were divided into three groups: Control (Cont), isoflurane (ISO) and MS-275 pre-treated groups. The rats were sacrificed following exposure to isoflurane and a cognitive test. The hippocampus of each animal was harvested for quantitative PCR, TUNEL staining and western blot analysis. Histone deacetylases (HDAC)-1, -2 and -3 exhibited a significant increase at the gene and protein expression levels, whereas negligible mRNA expressions were observed for genes HDAC 4-11 (P>0.05; compared with Cont). Pre-treatment with the HDAC inhibitor MS-275 significantly inhibited the increase in TUNEL-positive cells induced by isoflurane exposure (70.72% decrease; P
- Published
- 2019