Sevoflurane Induces Neurotoxicity in the Animal Model with Alzheimer’s Disease Neuropathology via Modulating Glutamate Transporter and Neuronal Apoptosis

• Published in: International journal of molecular sciences Vol. 23; no. 11; p. 6250
• Main Authors: Huang, Chunxia, Chu, John Man Tak, Liu, Yan, Kwong, Vivian Suk Wai, Chang, Raymond Chuen Chung, Wong, Gordon Tin Chun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.06.2022; MDPI
• Subjects: Alzheimer Disease - metabolism; Alzheimer's disease; Amino Acid Transport System X-AG - metabolism; Anesthesia; Anesthetics, Inhalation - adverse effects; Animals; Apoptosis; Brain-derived neurotrophic factor; Cognitive ability; Disease Models, Animal; Hippocampus - metabolism; Humans; Kinases; Mice; Nervous system; Neuropathology; Neurotoxicity; Neurotoxicity Syndromes - metabolism; Proteins; Rodents; Sevoflurane - adverse effects; cognitive function; apoptosis; sevoflurane; 3 × Tg mice; MAPK; glutamate transporter
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23116250

Perioperative neurocognitive disorders are frequently observed in postoperative patients and previous reports have shown that pre-existing mild cognitive impairment with accumulated neuropathology may be a risk factor. Sevoflurane is a general anesthetic agent which is commonly used in clinical practice. However, the effects of sevoflurane in postoperative subjects are still controversial, as both neurotoxic or neuroprotective effects were reported. The purpose of this study is to investigate the effects of sevoflurane in 3 × Tg mice, a specific animal model with pre-existing Alzheimer’s disease neuropathology. 3 × Tg mice and wild-type mice were exposed to 2 h of sevoflurane respectively. Cognitive function, glutamate transporter expression, MAPK kinase pathways, and neuronal apoptosis were accessed on day 7 post-exposure. Our findings indicate that sevoflurane-induced cognitive deterioration in 3 × Tg mice, which was accompanied with the modulation of glutamate transporter, MAPK signaling, and neuronal apoptosis in the cortical and hippocampal regions. Meanwhile, no significant impact was observed in wild-type mice. Our results demonstrated that prolonged inhaled sevoflurane results in the exacerbation of neuronal and cognitive dysfunction which depends on the neuropathology background.