Epigenetic Enhancement of Brain-Derived Neurotrophic Factor Signaling Pathway Improves Cognitive Impairments Induced by Isoflurane Exposure in Aged Rats

Ji, Mu‐Huo; Dong, Lin; Jia, Min; Liu, Wen-Xue; Zhang, Mingqiang; Ju, LinSha; Yang, Jiaojiao; Xie, Zhongcong; Yang, Jianjun

doi:10.1007/s12035-014-8659-z

Cited by 66 publications

(51 citation statements)

References 33 publications

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“…The BDNF‐TrkB signalling pathway is one of the downstream regulating targets of histone acetylation, so BDNF‐TrkB signalling pathway may be one of the underlying downstream mechanisms of learning and memory deficits induced by propofol exposure during early gestation. It is confirmed that HDAC2 up‐regulation will impair BDNF‐TrkB signalling pathway and results in cognitive impairments induced by isoflurane 54. Our previous study also verified the role of BDNF‐TrkB signalling pathway in the cognitive deficits induced by propofol during late pregnant stage 5.…”

Section: Discussionsupporting

confidence: 79%

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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Section: Discussionsupporting

confidence: 79%

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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“…All behavioral procedures were conducted at daytime from 2:00 PM to 5:00 PM in a sound-isolated room. All behavioral tests were recorded by the same investigator, who was blinded to the animal grouping as previously described [9,20]. Those animals were not subjected to further laboratory analysis.…”

Section: Behavioral and Cognitive Testsmentioning

confidence: 99%

Repeated Neonatal Sevoflurane Exposure-Induced Developmental Delays of Parvalbumin Interneurons and Cognitive Impairments Are Reversed by Environmental Enrichment

Wang

Sun

et al. 2016

Mol Neurobiol

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Parvalbumin (PV) interneurons are critically involved in the cognitive processes. Based on prior investigations that environmental enrichment reverses impaired cognition after anesthetic exposure, we proposed that environmental enrichment protects PV interneurons and thereby improves sevoflurane-induced cognitive impairments. Six-day-old C57BL/6 male mice were exposed to 3 % sevoflurane or 30 % oxygen/air 2 h daily for 3 days from postnatal day 6 (P6) to P8. The mice were randomly allocated to an enriched environment for 2 h daily between P8 and P90 or a standard environment. Western blotting and immunofluorescence were used for determining PV expression in the prefrontal cortex and hippocampus. In another set of experiments, cognitive tests were assessed by the open field test (P41), Morris water maze test (P54-60), and fear conditioning tests (P42-43 and P89-90). Exposure of neonatal mice to sevoflurane resulted in a reduced freezing response in the contextual test at P43 but not P90. The PV expression in these mice was decreased at P9, P14, P28, and P42, but not at ≥P60. No colocalization of caspase-3 and 5-bromo-2-deoxyuridine or caspase-3 and PV was observed, suggesting that caspase-independent pathways may be involved in the mediation of sevoflurane-induced down-regulation of PV. The sevoflurane-exposed mice that were placed in an enriched environment exhibited normal behavior and had PV interneurons that did not differ from those in the control mice at P42-43. Neonatal sevoflurane exposure induces a reduced freezing response in the contextual test at P43 and developmental delays in PV interneurons in the prefrontal cortex and hippocampus. Placement of the sevoflurane-exposed mice in an enriched environment can prevent these abnormalities.

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“…The FCT was performed as described by Zhang et al [20,21] with modifications. The training in FCT (XR-XC404, Shanghai Xin Soft Information Technology Co. Ltd.) was performed as follows.…”

Section: Fear Conditioning Test (Fct)mentioning

confidence: 99%

Mitochondria-Targeted Peptide Reverses Mitochondrial Dysfunction and Cognitive Deficits in Sepsis-Associated Encephalopathy

Zhang

Hao

et al. 2014

Mol Neurobiol

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Sepsis-associated encephalopathy (SAE) is associated with increased mortality, morbidity, and long-term cognitive impairments. Its pathophysiology remains to be determined and an effective pharmacologic treatment is lacking. The goal of this study was to investigate the effects of the mitochondria-targeted peptide SS-31 on mitochondrial function and cognitive deficits in SAE mice. C57BL/6 male mice were randomly divided into sham, sham + SS-31, cecal ligation and puncture (CLP), and CLP + SS-31 groups. Peptide SS-31 (5 mg/kg) was intraperitoneally administrated immediately after operation and afterwards once daily for six consecutive days. Surviving mice were subjected to behavioral tests and the hippocampus was collected for biochemical analysis 7 days after operation. The results showed that CLP resulted in high mortality rate and cognitive deficits, representative characteristics of SAE. A physiological mechanistic investigation revealed that mitochondrial function of hippocampus was severely impaired, coupled with reactive oxygen species (ROS) generation, triggering neuronal apoptosis and inflammation. Notably, administration of peptide SS-31 protected the integrity of mitochondria, reversed the mitochondrial dysfunction, inhibited the apoptosis resulting from the release of cytochrome c, diminished the response of inflammation, and ultimately reversed the behavior deficits in the SAE mice. In conclusion, our data demonstrate that daily treatment with mitochondria-targeted peptide SS-31 reduces mortality rate and ameliorates cognitive deficits, which is possibly through a mechanism of reversing mitochondrial dysfunction and partial inhibition of neuronal apoptosis and inflammation in the hippocampus of the SAE mice.

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Epigenetic Enhancement of Brain-Derived Neurotrophic Factor Signaling Pathway Improves Cognitive Impairments Induced by Isoflurane Exposure in Aged Rats

Cited by 66 publications

References 33 publications

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

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

Repeated Neonatal Sevoflurane Exposure-Induced Developmental Delays of Parvalbumin Interneurons and Cognitive Impairments Are Reversed by Environmental Enrichment

Mitochondria-Targeted Peptide Reverses Mitochondrial Dysfunction and Cognitive Deficits in Sepsis-Associated Encephalopathy

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