Internalization of GluA2 and the underlying mechanisms of cognitive decline in aged rats following surgery and prolonged exposure to sevoflurane

Hu, Nan; Wang, Miaomiao; Xie, Keliang; Wang, Haiyun; Wang, Chenxu; Wang, Chao; Li, Yize; Yu, Yonghao; Wang, Guolin

doi:10.1016/j.neuro.2015.05.010

Cited by 13 publications

(13 citation statements)

References 27 publications

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“…Indeed, sevoflurane was reported to induce high rates of postoperative cognitive dysfunction in comparison with other anesthetic agents (6). These dysfunctions may be associated with sevoflurane-induced neurotoxicity, which is documented in animals and humans (7)(8)(9). To date, the molecular mechanisms underlying sevoflurane-induced neurotoxicity have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Sevoflurane‑induced neurotoxicity is driven by OXR1 post‑transcriptional downregulation involving hsa‑miR‑302e

et al. 2018

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Sevoflurane is a common anesthetic agent used in surgical settings and previous studies have indicated that it exerts a neurotoxic effect. However, the molecular mechanism underlying this side effect is unknown. In addition, the human microRNA‑302 (hsa‑miR‑302) family members have been reported to be involved in neuronal cell development and biology. Thus, the present study aimed to investigate the potential implication of hsa‑miR‑302e in the sevoflurane‑induced cytotoxicity on human hippocampal cells (HN‑h). HN‑h cells were transfected with hsa‑miR‑302e mimic, hsa‑miR‑302e inhibitor or negative controls and subsequently exposed to different concentrations of sevoflurane. An MTT assay was used to assess the cytotoxicity of sevoflurane on HN‑h cells. Cell apoptosis was determined by flow cytometry. The levels of lactate dehydrogenase release, reactive oxygen species, lipid peroxidation and intracellular calcium (Ca2+) were additionally detected. Reverse transcription‑quantitative polymerase chain reaction and western blotting were conducted to determine mRNA and protein expression, respectively. A luciferase assay was performed for validating the targeting of OXR1 by hsa‑miR‑302e. The results indicated that sevoflurane induced a decrease in cell viability, malondialdehyde and reactive oxygen species production, lactate dehydrogenase release, intracellular Ca2+ production, calcium/calmodulin‑dependent protein kinase II phosphorylation and apoptosis. In addition, treatment with sevoflurane induced the expression of hsa‑miR‑302e while the expression of its target, oxidation resistance gene 1 (OXR1), was significantly downregulated. Inhibition of hsa‑miR‑302e expression protected neuronal cells from sevoflurane cytotoxicity. Mechanistic studies demonstrated that OXR1 was a direct target of hsa‑miR‑302e. Furthermore, the overexpression of OXR1 abolished the effect of sevoflurane on neuronal cells. The results of the present study indicated that sevoflurane exerts its neurotoxic effect by regulating the hsa‑miR‑302e/OXR1 axis. Therefore, the manipulation of the hsa‑miR‑302e/OXR1 pathway will be useful for preventing sevoflurane‑induced neurotoxicity.

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Section: Introductionmentioning

confidence: 99%

Sevoflurane‑induced neurotoxicity is driven by OXR1 post‑transcriptional downregulation involving hsa‑miR‑302e

et al. 2018

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“…[27] Furthermore, Arc activation of MEF2 as well as inhibition of phosphatidylinositol 3 kinase (PI3K)-AM-PAR-GluA2 contributed to postoperative cognition disorder. [39] Taken together, these data suggest that MEF2 plays a role in both synaptic plasticity and dementia diseases via its interaction with glutamatergic receptors.…”

Section: Mef2 and Dementia Diseasesmentioning

confidence: 85%

Myocyte Enhancer Factor-2 (MEF2) in Diseases of Central Nervous System: A Mini Review

Wang¹

2016

ERHM

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Myocyte enhancer factor-2 (MEF2), a family of transcription factors originally identified in muscles cells, was recently found to be expressed in the central nervous system. It is involved in the modulation of synapse elimination, a vital process that determines the fate and function of neurons. Recent studies suggested that MEF2 transcription factors are involved in synaptic plasticity, the molecular mechanism underlying learning and memory and other processes involved in dementia and neurodegenerative disease. This review summarizes recent advancements in understanding the role of MEF2 in neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, and Fragile X syndrome.

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“…B). At 72hr test point, the ANOVA analysis yielded a signi cant main effect of age [F (1,8) =4.6; p=0.05] and delay [F (5,40) =6.8, p<0.0001].…”

Section: Validation and Identi Cation Of Age-related Memory Impairmenmentioning

confidence: 99%

“…2G, p<0.05 for Bup high, p=0.058 for Bup low). The two-way ANOVA for repeated measures did not reveal a signi cant overall effect of analgesia treatments [F (5,47) =1.4; p=0.2] but there was a signi cant effect of delay [F (5, 235) = 53.3; p<0.0001] with no signi cant interaction. However, Fisher's LSD pairwise comparisons revealed the surgical group treated with Bup low or high were signi cantly impaired compared to MA controls ( Fig.…”

Section: Validation and Identi Cation Of Age-related Memory Impairmenmentioning

confidence: 99%

Paracetamol (acetaminophen) as potential first-choice analgesic in post-operative cognitive decline (POCD): Behavioral and molecular evidence in a middle-aged rat model

Garrone¹,

Durando²,

Prenderville³

et al. 2020

Preprint

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Post-operative cognitive dysfunction (POCD) is a debilitating clinical phenomenon in elderly patients. Management of pain in elderly is complicated because analgesic opiates elicit major side effects. In contrast, paracetamol (acetaminophen) has shown analgesic efficacy, no impact on cognition, and its side effects are well tolerated. We investigated the efficacy of paracetamol, compared to the opioid analgesic buprenorphine, in a model of POCD by investigating cognitive decline, allodynia, peripheral and hippocampal cytokines levels, and hippocampal microtubule dynamics as a key modulator of synaptic plasticity. A POCD model was developed in middle-aged (MA) rats by inducing a tibia fracture via orthopaedic surgery. Control MA rats did not undergo any surgery and only received isoflurane anaesthesia. We demonstrated that cognitive decline and increased allodynia following surgery was prevented in paracetamol-treated animals, but not in animals which were exposed to anesthesia alone or underwent the surgery and received buprenorphine. Behavioral alterations were associated with different peripheral cytokine changes between buprenorphine and paracetamol treated animals. Buprenorphine showed no central effects, while paracetamol showed modulatory effects on hippocampal cytokines and markers of microtubule dynamics which were suggestive of neuroprotection. Our data provide the first experimental evidence corroborating the use of paracetamol as first-choice analgesic in POCD.

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Internalization of GluA2 and the underlying mechanisms of cognitive decline in aged rats following surgery and prolonged exposure to sevoflurane

Cited by 13 publications

References 27 publications

Sevoflurane‑induced neurotoxicity is driven by OXR1 post‑transcriptional downregulation involving hsa‑miR‑302e

Sevoflurane‑induced neurotoxicity is driven by OXR1 post‑transcriptional downregulation involving hsa‑miR‑302e

Myocyte Enhancer Factor-2 (MEF2) in Diseases of Central Nervous System: A Mini Review

Paracetamol (acetaminophen) as potential first-choice analgesic in post-operative cognitive decline (POCD): Behavioral and molecular evidence in a middle-aged rat model

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