title: Isoflurane anesthesia promotes cognitive impairment by inducing expression of β-amyloid protein-related factors in the hippocampus of aged rats.
abstract: Isoflurane anesthesia has been shown to be responsible for cognitive impairment in Alzheimer's disease (AD) and development of AD in the older age groups. However, the pathogenesis of AD-related cognitive impairments induced by isoflurane anesthesia remains elusive. Thus, this study was designed to investigate the mechanism by which isoflurane anesthesia caused AD-related cognitive impairments. Aged Wistar rats were randomly divided into 6 groups (n = 12), 1 control group (CONT) and 5 isoflurane treated (ISO) groups (ISO 0, ISO 0.5D, ISO 1D, ISO 3D and ISO 7D). The CONT group inhaled 30% O2 for 2 h without any anesthesia. ISO groups were placed under anesthesia with 3% isoflurane and then exposed to 1.5% isoflurane delivered in 30% O2 for 2 h. Rats in each ISO group were then analyzed immediately (ISO 0) or at various time points (0.5, 1, 3 or 7 day) after this exposure. Cognitive function was assessed using the Morris water maze test. Protein levels of amyloid precursor protein (APP), β-site APP cleavage enzyme-1 (BACE-1) and Aβ42 peptide were analyzed in hippocampal samples by Western blot. β-Amyloid (Abeta) plaques were detected in hippocampal sections by Congo red staining. Compared with controls, all ISO groups showed increased escape latency and impaired spatial memory. Isoflurane increased APP mRNA expression and APP protein depletion, promoting Aβ42 overproduction, oligomerization and accumulation. However, isoflurane did not affect BACE-1 expression. Abeta plaques were observed only in those ISO groups sacrificed at 3 or 7 d. Our data indicate that aged rats exposed to isoflurane had increased APP mRNA expression and APP protein depletion, with Aβ42 peptide overproduction and oligomerization, resulting in formation of Abeta plaques in the hippocampus. Such effects might have contributed to cognitive impairments, including in spatial memory, observed in these rats after isoflurane anesthesia.
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guan
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
authors.forename: Li
authors.initials: L
authors.lastname: Luan
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
authors.forename: Qichao
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Fan
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000769:Anesthesia, Inhalation / Q000009:adverse effects; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000139:chemically induced* / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007530:Isoflurane / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D017208:Rats, Wistar; D065852:Spatial Memory / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D018685:Anesthetics, Inhalation; D007530:Isoflurane; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509281:Bace1 protein, rat