Up-regulation of Alzheimer’s disease-associated proteins may cause enflurane anesthesia induced cognitive decline in aged rats

Abstract

Isoflurane anesthesia can cause post-operative cognitive dysfunction in elderly patients. As an isomer of isoflurane, enflurane may also account for cognitive dysfunction. However, the mechanism of enflurane-induced cognitive dysfunction remains obscure. In this study, we investigated the effects of enflurane anesthesia on cognitive function and the possible roles of β-amyloid protein and phosphorylated tau protein in response to enflurane anesthesia in aged rats. After intraperitoneal injection of enflurane, the Morris water maze and the step-down passive avoidance tests were conducted to test the cognitive ability and memory. The enflurane group showed prolonged escape latency, extended space exploration time and increased number of errors at early stage after enflurane anesthesia, suggesting that enflurane should be responsible for the impairment of cognition in aged rats. In addition, we analyzed the expression level of β-amyloid and phosphorylation level of tau in the hippocampus by immunoblotting. Interestingly, the levels of β-amyloid and phosphorylated tau in the hippocampus increased significantly at early stage and then restored to pre-anesthetic levels. Taken together, our results suggest that increasing of β-amyloid and phosphorylation of tau are important to cause cognitive decline in aged rats during initial stage after enflurane anesthesia.

Increased extrasynaptic GluN2B expression is involved in cognitive impairment after isoflurane anesthesia

“…Stratmann et al identified that aged rats exposed to isoflurane showed no evidence of ongoing cell death, impaired hippocampal neurogenesis, or long-term cognitive impairment ( 24 ). Cognitive impairment by anesthetics in the aging brain manifest certain temporary characteristics of Alzheimer's disease, such as elevated Aβ production and τ hyperphosphorylation ( 25 ), which caused synaptic dysfunction without obvious neural loss at the early phase of this disease ( 26 – 30 ). Evidence suggests that inhibitory ionotropic receptors, α-5 subunit containing γ aminobutyric acid-A receptors (α-5GABAARs) can be upregulated and maintain a persistent inhibitory current for 1 week even after a single dosage of etomidate ( 5 ).…”

Effects of general anesthetics on the cognitive function of pediatric patients: A review

“…flurane and suggested that it may cause postoperative cognitive dysfunction [38]. Liu et al revealed that this may be related to the significantly elevated levels of β-amyloid and phosphorylated tau in the hippocampus at an early stage [39]. The targets of various anesthetics and the possible toxicity are shown in Table 1.…”

Effects of General Anesthetics on Synaptic Transmission and Plasticity

“…Accumulation of brain Aβ plaque burden was also recapitulated in vivo in Alzheimer’s disease mice with halothane exposure [ 442 ]. Moreover, in wild- type rodents and in Alzheimer’s disease model mice, sevoflurane, isoflurane, or enflurane induced Aβ oligomerization [ 443 ], tau hyperphosphorylation and cognitive decline [ 444 - 447 ] mediated by Akt and ERK activation [ 448 , 449 ].…”