Cognitive Impairment and Endoplasmic Reticulum Stress Induced by Repeated Short-Term Sevoflurane Exposure in Early Life of Rats

Shen, Fei; Song, Yingcai; Guo, Fei; Xu, Zhendong; Li, Qian; Zhang, Bing; Ma, Yanhe; Zhang, Yueqi; Lin, Rong; Li, Yang; Liu, Zhiqiang

doi:10.3389/fpsyt.2018.00332

Cited by 21 publications

(21 citation statements)

References 38 publications

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“…Furthermore, excessive stimulation impairs calcium homeostasis in the neurons, thus affecting the normal functioning of ER and results in the accumulation of the misfolded proteins (Bhardwaj et al, 2017;Prentice et al, 2015). Thus, this study was an attempt to further association Shen et al, 2018). Since overstimulation of neurons and glutamate receptors in the central nervous system (CNS) plays a key role in the learning and memory of the animals (Huo et al, 2015), therefore motor and memory impairments are believed to be get affected following ER stress (Shen et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, this study was an attempt to further association Shen et al, 2018). Since overstimulation of neurons and glutamate receptors in the central nervous system (CNS) plays a key role in the learning and memory of the animals (Huo et al, 2015), therefore motor and memory impairments are believed to be get affected following ER stress (Shen et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

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AMPA induced cognitive impairment in rats: Establishing the role of endoplasmic reticulum stress inhibitor, 4‐PBA

Bhardwaj

Sharma

et al. 2021

J of Neuroscience Research

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Glutamate excitotoxicity and endoplasmic reticulum (ER) recently have been found to be instrumental in the pathogenesis of various neurodegenerative diseases. However, the paucity of literature deciphering the inter-linkage among glutamate receptors, behavioral alterations, and ER demands thorough exploration. Reckoning the aforesaid concerns, a prospective study was outlined to delineate the influence of ER stress inhibition via 4-phenylbutyric acid (PBA) on α-amino-3-hydroxy-5-methyl-4isoxazole propionic acid (AMPA) excitotoxicity-induced behavioral aspects and possible ER stress-glutamate linkage. Male SD rats were randomly divided into four groups namely sham (surgical control+vehicle, group 1), AMPA-induced excitotoxic group 2 receive a single intra-hippocampal injection of 10 mM AMPA, group 3 received AMPA along with PBA (i.p, 100 mg/kg body weight) for 15 days, and group 4 received PBA alone. Behavioral analyses were performed prior to the sacrifice of animals and hippocampus was extracted thereafter for further analysis. AMPA-induced excitotoxicity exhibited significant impairment of locomotion as well as cognitive functions. The levels of neurotransmitters such as dopamine, homo vanillic acid (HVA), norepinephrine, and serotonin were reduced accompanied by reduced expression of GLUR1 and GLUR4 (glutamate receptor) as well as loss of neurons in different layers of hippocampus. ER stress markers were upregulated upon AMPA excitotoxicity.However, chemical chaperone PBA supplementation remarkably mitigated the behavioral alterations along with expression of glutamate and ER stress intermediates/ markers in AMPA excitotoxic animals. Therefore, the present exploration convincingly emphasizes the significance of ER stress and its inhibition via PBA in combating cognitive impairment as well as improving locomotion in excitotoxic animals.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

AMPA induced cognitive impairment in rats: Establishing the role of endoplasmic reticulum stress inhibitor, 4‐PBA

Bhardwaj

Sharma

et al. 2021

J of Neuroscience Research

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“…Thus, the UPR may represent one of the most important cellular adaptive mechanisms to injury. We were the first to report that fetal exposure to inhalational anesthetics causes ER stress and neuronal cell death [34]; since then, several other papers have confirmed that general anesthesia causes ER stress [75][76][77][78][79][80][81].…”

Section: Discussionmentioning

confidence: 99%

Conflicting Actions of Inhalational Anesthetics, Neurotoxicity and Neuroprotection, Mediated by the Unfolded Protein Response

Kokubun

Jin

Komita

et al. 2020

IJMS

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Preclinical studies have shown that exposure of the developing brain to inhalational anesthetics can cause neurotoxicity. However, other studies have claimed that anesthetics can exert neuroprotective effects. We investigated the mechanisms associated with the neurotoxic and neuroprotective effects exerted by inhalational anesthetics. Neuroblastoma cells were exposed to sevoflurane and then cultured in 1% oxygen. We evaluated the expression of proteins related to the unfolded protein response (UPR). Next, we exposed adult mice in which binding immunoglobulin protein (BiP) had been mutated, and wild-type mice, to sevoflurane, and evaluated their cognitive function. We compared our results to those from our previous study in which mice were exposed to sevoflurane at the fetal stage. Pre-exposure to sevoflurane reduced the expression of CHOP in neuroblastoma cells exposed to hypoxia. Anesthetic pre-exposure also significantly improved the cognitive function of adult wild-type mice, but not the mutant mice. In contrast, mice exposed to anesthetics during the fetal stage showed cognitive impairment. Our data indicate that exposure to inhalational anesthetics causes endoplasmic reticulum (ER) stress, and subsequently leads to an adaptive response, the UPR. This response may enhance the capacity of cells to adapt to injuries and improve neuronal function in adult mice, but not in developing mice.

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“…have shown that repeated exposure to sevoflurane during pregnancy inhibits neuronal migration and leads to defective neuronal migration in offspring, suggesting that sevoflurane affects the brain development (Chai, 2019). Sevoflurane can also induce neuronal apoptosis in newborn mice or rats and cause cognitive dysfunction by activating the endoplasmic reticulum stress pathway (Liu et al., 2017; Shen, 2018). In addition to the endoplasmic reticulum, mitochondria also play an important role in the regulation of apoptosis.…”

Section: Sevoflurane Neuroapoptosis and Neuroinflammationmentioning

confidence: 99%

Prenatal sevoflurane exposure: Effects of iron metabolic dysfunction on offspring cognition and potential mechanism

Zuo

Chang

Thirupathi

et al. 2020

Intl J of Devlp Neuroscience

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For decades, the neurotoxicity caused by anesthetics in mammalian brain development has gained increasing attention. Exposure to anesthetics leads to neurotoxicity and apoptosis of nerve cells, which in turn induces cognitive dysfunction. Although most of the data came from animal studies, general anesthetics have been shown to have adverse effects on cognitive function in infants and young children in recent years. This concern has led to a number of retrospective studies that observed an association between general anesthesia in pregnant women and neurobehavioral problems in fetuses or offspring. Every year, many pregnant women undergo non‐obstetric anesthesia due to various reasons such as traffic accidents, fetal interventions, acute appendicitis, symptomatic cholelithiasis, and trauma. A matter of concern for these pregnant women is whether anesthesia has a detrimental effect on fetal brain development in the womb and whether the fetus has cognitive impairment after birth. In humans, the association of anesthetic exposure in infants with the long‐term impairment of neurologic functions has been reported in several retrospective clinical studies. Recently, we have found that sevoflurane anesthesia during pregnancy in mice‐induced cognitive impairment in the offspring by causing iron deficiency and inhibiting myelinogenesis. Sevoflurane is a commonly used general anesthetic in the hospitals, which can induce neurotoxicity and cause cognitive impairment in fetuses, infants, children, and adults. However, the exact mechanism of sevoflurane‐induced damage to the central nervous system (CNS) is not fully understood. Based on our recent results, this paper reviewed the effects of sevoflurane on cognitive impairment and pathological changes such as neurogenesis, neuronal apoptosis, and iron metabolism dysfunction in the offspring.

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Cognitive Impairment and Endoplasmic Reticulum Stress Induced by Repeated Short-Term Sevoflurane Exposure in Early Life of Rats

Cited by 21 publications

References 38 publications

AMPA induced cognitive impairment in rats: Establishing the role of endoplasmic reticulum stress inhibitor, 4‐PBA

AMPA induced cognitive impairment in rats: Establishing the role of endoplasmic reticulum stress inhibitor, 4‐PBA

Conflicting Actions of Inhalational Anesthetics, Neurotoxicity and Neuroprotection, Mediated by the Unfolded Protein Response

Prenatal sevoflurane exposure: Effects of iron metabolic dysfunction on offspring cognition and potential mechanism

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