Aberrantly expressed long noncoding RNAs are involved in sevoflurane-induced developing hippocampal neuronal...

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Volatile anesthetics like sevoflurane can cause apoptosis in the developing brain.
• Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in neural development and disease.
• The precise molecular pathways of sevoflurane-induced neurotoxicity are not fully understood.

Purpose of the Study:

• To investigate the involvement of lncRNAs in sevoflurane-induced hippocampal apoptosis in neonatal mice.
• To identify specific lncRNAs and their target genes affected by sevoflurane exposure.
• To elucidate the molecular mechanisms linking lncRNAs to anesthetic-induced neurotoxicity.

Main Methods:

• Utilized lncRNA-mRNA microarray analysis in P7 mice exposed to sevoflurane.
• Performed quantitative real-time PCR (qRT-PCR) to validate microarray findings.
• Employed a co-expression network (CNC) analysis to explore lncRNA-mRNA correlations.

Main Results:

• Sevoflurane exposure induced significant hippocampal apoptosis and morphological changes.
• Microarray analysis identified differentially expressed lncRNAs and mRNAs, including ENSMUST00000136025 and Bcl2l11 (BIM).
• Upregulated ENSMUST00000136025 showed a positive correlation with BIM, alongside increased pro-apoptotic proteins (BIM, Bax) and decreased anti-apoptotic proteins (Bcl-2).

Conclusions:

• Aberrantly expressed lncRNAs contribute to sevoflurane-induced hippocampal apoptosis.
• The lncRNA ENSMUST00000136025 likely promotes BIM overexpression, driving mitochondria-mediated apoptosis.
• These findings enhance understanding of the molecular mechanisms underlying sevoflurane neurotoxicity.