Maternal Exposure of Rats to Isoflurane during Late Pregnancy Impairs Spatial Learning and Memory in the Offspring by Up-Regulating the Expression of Histone Deacetylase 2

Luo, Foquan; Huang, Yan; Zhao, Wei; Zuo, Zhiyi; Qi, Yu; Liu, Zhiyi; Lin, Jiamei; Feng, Yunlin; Li, Binda; Wu, Liuqin; Xu, Lin

doi:10.1371/journal.pone.0160826

Cited by 25 publications

(27 citation statements)

References 56 publications

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“…It is relevant that HDAC2 does not interact with NF‐κB directly but can regulate NF‐κB activity through its association with HDAC1 . By contrast, several other studies have found that repeated isoflurane exposure enhances the expression of inflammatory cytokines in the brain with HDAC2 upregulation . Our results combined with those of previous studies support the idea that isoflurane‐induced histone deacetylation and inhibition of NF‐κB nuclear translocation and inflammatory genes could contribute to the anti‐inflammatory properties of isoflurane.…”

Section: Discussionsupporting

confidence: 81%

HDAC1 and HDAC2 regulate anti‐inflammatory effects of anesthetic isoflurane in human monocytes

et al. 2020

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Pre-exposure to volatile anesthetics inhibits inflammation induced by various stimuli, including surgical procedures and ischemia. We hypothesize that volatile anesthetics may induce anti-inflammatory effects via a mechanism involving regulation of histone deacetylases (HDACs). Pre-exposure of 1.5% isoflurane for 0.5 h induced anti-inflammatory effects [measured by cytokine production of tumor necrosis factor-ɑ, interleukin-8 (IL-8) and IL-1b] in both human THP-1 cells and primary human peripheral blood monocytes stimulated by lipopolysaccharide. In human THP-1 cells, coadministration of the HDAC inhibitor trichostatin A (TSA) blocked the isoflurane-induced antiinflammatory effects. TSA also blocked isoflurane-upregulated HDAC1-3 expression and isoflurane-reduced nuclear translocation of p65 and p50 subunits of nuclear factor-jB (NF-jB). The ability of isoflurane to reduce NF-jB nuclear translocation and proinflammatory responses in the cell line was blocked by gene silencing of HDAC1 and HDAC2, but not by gene silencing of HDAC3. A coimmunoprecipitation assay demonstrated that the decreased interaction between HDAC1 and HDAC2 through lipopolysaccharide was restored by isoflurane pretreatment. These findings were validated in primary human peripheral blood monocytes wherein gene silencing of HDAC1 and HDAC2 resulted in increased cytokine production and NF-jB nuclear translocation induced by isoflurane pre-exposure and lipopolysaccharide stimulation. These results indicate that anti-inflammatory effects of the volatile anesthetic isoflurane in human monocytes involve regulation of HDAC1 and HDAC2.

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Section: Discussionsupporting

confidence: 81%

HDAC1 and HDAC2 regulate anti‐inflammatory effects of anesthetic isoflurane in human monocytes

et al. 2020

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“…Abolished the memory impairments in connection with neurodegeneration 35. Our earlier study suggested that maternal isoflurane anaesthesia during third trimester impairs the spatial learning and memory of the offspring rats, and its mechanism in connection with the up‐regulation of HDAC2 mRNA and subsequent inhibits the expression of CREB mRNA and NR2B, while HDAC2 inhibition reversed these changes 30. Consistent to our previous study, our results suggest that maternal propofol anaesthesia on E7 impairs learning and memory in offspring rats, causes the overexpression of HDAC2 and inhibits the acetylation of H3K14 and H4K12, and these effects were reversed by SAHA.…”

Section: Discussionmentioning

confidence: 94%

“…Spatial learning and memory were assessed by the MWM test from post‐natal day 30 (P30) to P36 according to previously described5, 30 with SLY‐WMS Morris water maze test system (Beijing Sunny Instruments Co. Ltd., Beijing, China). Briefly, the trials start at 9 o'clock in the morning in the MWM system with the pool was filled with water to a height of 1.0 cm above the top of a 15‐cm‐diameter platform, in the second quadrant (target quadrant), and the water maintained at 24 ± 1°C.…”

Section: Methodsmentioning

confidence: 99%

Propofol exposure during early gestation impairs learning and memory in rat offspring by inhibiting the acetylation of histone

Lin

Wang

Feng

et al. 2018

J Cellular Molecular Medi

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Propofol is widely used in clinical practice, including non‐obstetric surgery in pregnant women. Previously, we found that propofol anaesthesia in maternal rats during the third trimester (E18) caused learning and memory impairment to the offspring rats, but how about the exposure during early pregnancy and the underlying mechanisms? Histone acetylation plays an important role in synaptic plasticity. In this study, propofol was administered to the pregnant rats in the early pregnancy (E7). The learning and memory function of the offspring were tested by Morris water maze (MWM) test on post‐natal day 30. Two hours before each MWM trial, histone deacetylase 2 (HDAC2) inhibitor, suberoylanilide hydroxamic acid (SAHA), Senegenin (SEN, traditional Chinese medicine), hippyragranin (HGN) antisense oligonucleotide (HGNA) or vehicle were given to the offspring. The protein levels of HDAC2, acetylated histone 3 (H3) and 4 (H4), cyclic adenosine monophosphate (cAMP) response element‐binding protein (CREB), N‐methyl‐D‐aspartate receptor (NMDAR) 2 subunit B (NR2B), HGN and synaptophysin in offspring's hippocampus were determined by Western blot or immunofluorescence test. It was discovered that infusion with propofol in maternal rats on E7 leads to impairment of learning and memory in offspring, increased the protein levels of HDAC2 and HGN, decreased the levels of acetylated H3 and H4 and phosphorylated CREB, NR2B and synaptophysin. HDAC2 inhibitor SAHA, Senegenin or HGN antisense oligonucleotide reversed all the changes. Thus, present results indicate exposure to propofol during the early gestation impairs offspring's learning and memory via inhibiting histone acetylation. SAHA, Senegenin and HGN antisense oligonucleotide might have therapeutic value for the adverse effect of propofol.

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“…Offspring of pregnant rat exposed with isoflurane anesthesia showed impaired spatial memory with increase in HDAC2 and decrease in CREB and NR2B expression in the hippocampus. Further, treatment with HDAC inhibitor Suberoylanilide hydroxamic acid (SAHA) ameliorated the effect of isoflurane and recovered memory in offspring [ 89 ]. Maternal separation is an early life stress which has adverse effect on nervous system of the young and impaired cognitive functions including learning and memory.…”

Section: Chromatin Modifications and Regulation Of Memorymentioning

confidence: 99%

Epigenetic Regulation of Memory-Therapeutic Potential for Disorders

Singh

Srivas

Thakur

2017

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Background: Memory is a vital function which declines in different physiological and pathological conditions such as aging and neurodegenerative diseases. Research in the past has reported that memory formation and consolidation require the precise expression of synaptic plasticity genes. However, little is known about the regulation of these genes. Epigenetic modification is now a well established mechanism that regulates synaptic plasticity genes and neuronal functions including memory. Therefore, we have reviewed the epigenetic regulation of memory and its therapeutic potential for memory dysfunction during aging and neurological disorders.Method: Research reports and online contents relevant to epigenetic regulation of memory during physiological and pathological conditions have been compiled and discussed.Results: Epigenetic modifications include mainly DNA methylation and hydroxymethylation, histone acetylation and methylation which involve chromatin modifying enzymes. These epigenetic marks change during memory formation and impairment due to dementia, aging and neuro-degeneration. As the epigenetic modifications are reversible, they can be modulated by enzyme inhibitors leading to the recovery of memory.Conclusion: Epigenetic modifications could be exploited as a potential therapeutic target to recover memory disorders during aging and pathological conditions.

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Maternal Exposure of Rats to Isoflurane during Late Pregnancy Impairs Spatial Learning and Memory in the Offspring by Up-Regulating the Expression of Histone Deacetylase 2

Cited by 25 publications

References 56 publications

HDAC1 and HDAC2 regulate anti‐inflammatory effects of anesthetic isoflurane in human monocytes

HDAC1 and HDAC2 regulate anti‐inflammatory effects of anesthetic isoflurane in human monocytes

Propofol exposure during early gestation impairs learning and memory in rat offspring by inhibiting the acetylation of histone

Epigenetic Regulation of Memory-Therapeutic Potential for Disorders

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