Docosahexaenoic Acid Rescues Synaptogenesis Impairment and Long-Term Memory Deficits Caused by Postnatal Multiple Sevoflurane Exposures

Tao, Guorong; Luo, Yan; Xue, Qingsheng; Li, Guohui; Tan, Yongchang; Xiao, Jinglei; Yu, Bo

doi:10.1155/2016/4062579

Cited by 15 publications

(8 citation statements)

References 25 publications

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“…At this age point, it is not so clear that the pathology would provoke significant alteration of synaptic markers, so the effect observed should be only related to the dietary effect. DHA has been described to increase synaptic proteins such as synaptophysin and PSD95 [77]. Our results showed no evident modifications of the analyzed proteins, although the levels of phospho-synapsin were strongly affected by lower dietary ω-6/ω-3 ratio in females [29,34].…”

Section: Discussioncontrasting

confidence: 47%

Diets with Higher ω-6/ω-3 Ratios Show Differences in Ceramides and Fatty Acid Levels Accompanied by Increased Amyloid-Beta in the Brains of Male APP/PS1 Transgenic Mice

Ordóñez-Gutiérrez

Fabriás

Casas

2021

IJMS

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Senile plaque formation as a consequence of amyloid-β peptide (Aβ) aggregation constitutes one of the main hallmarks of Alzheimer’s disease (AD). This pathology is characterized by synaptic alterations and cognitive impairment. In order to either prevent or revert it, different therapeutic approaches have been proposed, and some of them are focused on diet modification. Modification of the ω-6/ω-3 fatty acids (FA) ratio in diets has been proven to affect Aβ production and senile plaque formation in the hippocampus and cortex of female transgenic (TG) mice. In these diets, linoleic acid is the main contribution of ω-6 FA, whereas alpha-linoleic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) are the contributors of ω-3 FA. In the present work, we have explored the effect of ω-6/ω-3 ratio modifications in the diets of male double-transgenic APPswe/PS1ΔE9 (AD model) and wild-type mice (WT). Amyloid burden in the hippocampus increased in parallel with the increase in dietary ω-6/ω-3 ratio in TG male mice. In addition, there was a modification in the brain lipid profile proportional to the ω-6/ω-3 ratio of the diet. In particular, the higher the ω-6/ω-3 ratio, the lower the ceramides and higher the FAs, particularly docosatetraenoic acid. Modifications to the cortex lipid profile was mostly similar between TG and WT mice, except for gangliosides (higher levels in TG mice) and some ceramide species (lower levels in TG mice).

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Section: Discussioncontrasting

confidence: 47%

Diets with Higher ω-6/ω-3 Ratios Show Differences in Ceramides and Fatty Acid Levels Accompanied by Increased Amyloid-Beta in the Brains of Male APP/PS1 Transgenic Mice

Ordóñez-Gutiérrez

Fabriás

Casas

2021

IJMS

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“…Normal expression of JunB has been shown to be essential to genetic stability, and is implicated in cell survival, cell proliferation, and programmed cell death and senescence [33]. Research has shown that exposure to sevoflurane results in decreased synaptic density, filopodia length, neuronal spines, and spine density of apical dendrites [12,43,44]. Inappropriate transcription of junB and arc may underlie dysregulated synaptic growth.…”

Section: Discussionmentioning

confidence: 99%

“…Exposure to the inhalational anesthetic sevoflurane during critical stages of brain development induces widespread neuronal apoptosis in various mammalian species [6][7][8][9]. Sevoflurane-induced neurotoxicity and synaptic morphological changes are associated with behavioral deficits exhibited as juveniles and adults [10][11][12]. Importantly, cognitive deficits have been reported in unexposed offspring of dams exposed in utero, suggesting that exposure to anesthetics may result in a transgenerational epigenetic modifications [13].…”

Section: Introductionmentioning

confidence: 99%

Sevoflurane Exposure Results in Sex-Specific Transgenerational Upregulation of Target IEGs in the Subiculum

et al. 2019

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Large body of animal work and emerging clinical findings have suggested that early exposure to anesthetics may result in increased risk of learning disabilities and behavioral impairments [1][2][3][4]. Recent studies have begun to investigate anesthesia-induced epigenetic modifications to elucidate their role in behavioral and neurodevelopmental abnormalities. Here we examine sevofluraneinduced transgenerational modifications of subicular neuronal DNA methylation and expression of immediate early genes (lEGs), arc and junB, crucial to synaptic plasticity and normal neuronal development. We show that 6h sevoflurane exposure in postnatal day 7 rat pups resulted in a decrease in neuronal 5-methycytosine, indicating reduced DNA methylation. This effect is transgenerationally expressed in offspring born to exposed mothers which is of importance considering that decreased DNA methylation in the brain has been linked with functional decline in learning and memory [5]. We further show that sevoflurane exposure induces upregulation of Arc and JunB mRNA expression, 42.7% and 35.2%, respectively. Transgenerational changes in Arc and JunB mRNA were sexually dimorphic only occurring in males born to exposed females, expressed as upregulation of Arc and JunB mRNA, 71.6% and 74.0%, respectively. We further investigated correlation between altered arc promoter methylation and observed upregulation of Arc mRNA and observed that sevoflurane reduced methylation in the 5-upstream promoter region of females exposed to sevoflurane. Transgenerational hypomethylation and modifications to lEGs crucial to synaptic plasticity, observed following neonatal sevoflurane exposure could contribute to morphological and cognitive deficits known to occur with neonatal sevoflurane exposure.

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“…Specifically, sevoflurane has been shown to induce cellular apoptosis [8–13], endoplasmic reticulum stress [9, 14–16], synaptogenesis impairment [17–20], mitochondrial dysfunction [18, 20] and neuroinflammation [9, 21] in vitro and in vivo in mice. These effects may then lead to cognitive impairment in young mice [22].…”

Section: Introductionmentioning

confidence: 99%

Sevoflurane induces cognitive impairment in young mice via autophagy

et al. 2019

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Background Anesthesia may induce neurotoxicity and neurocognitive impairment in young mice. However, the underlying mechanism remains largely to be determined. Meanwhile, autophagy is involved in brain development and contributes to neurodegenerative diseases. We, therefore, set out to determine the effects of sevoflurane on autophagy in the hippocampus of young mice and on cognitive function in the mice. Methods Six day-old mice received 3% sevoflurane, for two hours daily, on postnatal days (P) 6, 7 and 8. We then decapitated the mice and harvested the hippocampus of the young mice at P8. The level of LC3, the ratio of LC3-II to LC3-I, and SQSTM1/p62 level associated with the autophagy in the hippocampus of the mice were assessed by using Western blotting. We used different groups of mice for behavioral testing via the Morris Water Maze from P31 to P37. Results The anesthetic sevoflurane increased the level of LC3-II and ratio of LC3-II/LC3-I, decreased the p62 level in the hippocampus of the young mice, and induced cognitive impairment in the mice. 3-Methyladenine, the inhibitor of autophagy, attenuated the activation of autophagy and ameliorated the cognitive impairment induced by sevoflurane in the young mice. Conclusion These data showed that sevoflurane anesthesia might induce cognitive impairment in the young mice via activation of autophagy in the hippocampus of the young mice. These findings from the proof of concept studies have established a system and suggest the role of autophagy in anesthesia neurotoxicity and cognitive impairment in the young mice, pending further investigation.

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Docosahexaenoic Acid Rescues Synaptogenesis Impairment and Long-Term Memory Deficits Caused by Postnatal Multiple Sevoflurane Exposures

Cited by 15 publications

References 25 publications

Diets with Higher ω-6/ω-3 Ratios Show Differences in Ceramides and Fatty Acid Levels Accompanied by Increased Amyloid-Beta in the Brains of Male APP/PS1 Transgenic Mice

Diets with Higher ω-6/ω-3 Ratios Show Differences in Ceramides and Fatty Acid Levels Accompanied by Increased Amyloid-Beta in the Brains of Male APP/PS1 Transgenic Mice

Sevoflurane Exposure Results in Sex-Specific Transgenerational Upregulation of Target IEGs in the Subiculum

Sevoflurane induces cognitive impairment in young mice via autophagy

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