Suberoylanilide hydroxamic acid (SAHA) alleviates the learning and memory impairment in rat offspring caused by maternal sevoflurane exposure during late gestation

Abstract

Recent studies have shown that sevoflurane can cause long-term neurotoxicity and learning and memory impairment in developing and progressively neurodegenerative brains. Sevoflurane is a widely used volatile anesthetic in clinical practice. Late gestation is a rapidly developing period in the fetal brain, but whether sevoflurane anesthesia during late gestation affects learning and memory of offspring is not fully elucidated. Histone deacetylase 2 (HDAC2) plays an important regulatory role in learning and memory. This study examined the effect of maternal sevoflurane exposure on learning and memory in offspring and the underlying role of HDAC2. The Morris water maze (MWM) test was used to evaluate learning and memory function. Q-PCR and immunofluorescence staining were used to measure the expression levels of genes related to learning and memory. The results showed that sevoflurane anesthesia during late gestation impaired learning and memory in offspring rats (e.g., showing increase of the escape latency and decrease of the platform-crossing times and target quadrant traveling time in behavior tests) and upregulated the expression of HDAC2, while downregulating the expression of the cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) and the N-methyl-D-aspartate receptor 2 subunit B (NR2B) mRNA and protein in the hippocampus of offspring in a timedependent manner. HDAC2 inhibitor suberoylanilide hydroxamic acid (SAHA) treatment alleviated all of these changes in offspring rats. Therefore, the present study indicates that sevoflurane exposure during late gestation impairs offspring rat's learning and memory via upregulation of the expression of HDAC2 and downregulation of the expression of CREB and NR2B. SAHA can alleviate these impairments.

Research progress on molecular mechanisms of general anesthetic-induced neurotoxicity and cognitive impairment in the developing brain

“…Histone deacetylase 2 (HDAC2) is a protein that regulates the transcription of memory-related genes. The study found that rats exposed to sevoflurane impaired cognitive functions such as learning and memory in offspring mice by upregulating HDAC2, and inhibition of HDAC2 attenuated these impairments ( 63 ). This suggests that HDAC2 may mediate the process of neurotoxicity and cognitive damage induced by general anesthetics in newborn brain cells, and it can reduce the neurotoxicity and cognitive damage induced by general anesthetics by inhibiting the expression of HDAC2.…”

MicroRNA-495 suppresses pre-eclampsia via activation of p53/PUMA axis

“…Bioinformatics prediction showed a targeting association between miR-495 and histone deacetylase 2 (HDAC2). HDACs play critical roles in remodeling chromatin and regulating gene- and cellular-signaling pathways, in which HDAC2 is important for learning and memory abilities during late gestation [ 14 , 15 ]. Notably, a decline in HDAC2 expression is seen in placental tissues of severe PE patients [ 16 ].…”

Expression of histone deacetylase 2 in tracheal stenosis models and its relationship with tracheal granulation tissue proliferation

“…Glucocorticoids suppress the multiple inflammatory genes that are activated in asthma via reversing the histone acetylation of activated inflammatory genes, and this is initiated by the interaction of ligand-bound glucocorticoid receptors with coactivator molecules and the recruitment of HDAC2 to the activated inflammatory gene transcription complex (14). Vorinostat is a class I HDAC inhibitor, which has been demonstrated to exhibit a strong inhibitory effect on HDAC2 and is clinically used to treat malignant tumors (15)(16)(17). In the present study, models of tracheal stenosis after injury were established and drugs were administered to positively and negatively regulate the expression of HDAC2.…”