lncRNA BDNF-AS Attenuates Propofol-Induced Apoptosis in HT22 Cells by Modulating the BDNF/TrkB Pathway

Abstract

Propofol is widely used as an intravenous anesthetic in clinical practice. Previous studies have indicated that propofol induces apoptosis in neurons. Brain-derived neurotrophic factor (BDNF), a neurotrophic factor, is associated with neuronal apoptosis. BDNF-AS, a relatively conserved long non-coding RNA, can reverse the transcription of BDNF. This study aimed to investigate the involvement of BDNF-AS in propofol-induced apoptosis in HT22 cells. HT22 cells were treated with various concentrations of propofol at different time points. BDNF-AS was silenced using BDNF-AS-targeting siRNA. TrkB was antagonized by the TrkB inhibitor, ANA-12. Flow cytometry, quantitative reverse-transcription PCR, and western blotting were performed to analyze apoptosis and the expression of genes and proteins, respectively. In propofol-treated HT22 cells, BDNF-AS was upregulated, and BDNF was downregulated in a time- and dose-dependent manner. BDNF-AS downregulation mediated by siRNA mitigated apoptosis, upregulated the expression of Bcl-2, and downregulated the expression of Bax and caspase-3, 7, and 9. ANA-12 downregulated the expression of Bcl-2, upregulated the expression of Bax and caspase-3, 7, and 9, and increased apoptosis. Our study implied that inhibition of BDNF-AS can decrease propofol-induced apoptosis by activating the BDNF/TrkB pathway. Thus, the BDNF-AS-BDNF/TrkB signaling pathway may be a valuable target for treating propofol-induced neurotoxicity.

Anaesthesia and brain development: a review of propofol-induced neurotoxicity in pediatric populations

“…41 microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have been found to be involved in the neurotoxicity process of propofol. 42,43 MicroRNAs (miRNAs) are endogenous noncoding RNA molecules with a length of approximately 22 nucleotides that regulate cellular processes by inhibiting the translation of messenger RNAs. 44 MiRNAs have become a research hotspot on the neurotoxicity of anesthetics in recent years.…”

Propofol-Induced Developmental Neurotoxicity: From Mechanisms to Therapeutic Strategies

“…Uncleaved proBDNF preferentially binds to p75 neurotrophin receptor (p75NTR), whereas mature BDNF may preferentially bind to tyrosine kinase receptor B (TrkB). , Uncleaved proBDNF binds to the p75NTR and activates RhoA, a small GTPase that regulates actin cytoskeleton polymerization, resulting in inhibition of axonal elongation, growth cone collapse, and apoptosis. − A previous study demonstrated that propofol exposure to developing neurons isolated from DIV 4–7 BALB/c mice induces apoptosis through the p75NTR/RhoA/RhoA kinase (ROCK) pathway . In addition, another study found that propofol exposure suppresses mature BDNF protein expression in a dose- and time-dependent manner and increases apoptosis of HT22 mouse hippocampal neuronal cells by inhibiting the BDNF/TrkB pathway …”

“…78 In addition, another study found that propofol exposure suppresses mature BDNF protein expression in a dose-and time-dependent manner and increases apoptosis of HT22 mouse hippocampal neuronal cells by inhibiting the BDNF/TrkB pathway. 79 BDNF can be almost secreted by astrocytes in a paracrine fashion. 80 Astrocytes, the largest population of glial cells, powerfully control the formation, maturation, function, and elimination of synapses through various secreted and contactmediated signals.…”

FGF2 gene's antisense protein, NUDT6, plays a depressogenic role by promoting inflammation and suppressing neurogenesis without altering FGF2 signalling

“…Both FGF2 and BDNF have natural antisense transcripts, RNA molecules that are transcribed from the opposite strand of protein‐coding genes, and are suggested to regulate the transcription of their sense strand (Modarresi et al., 2012). Supporting this, BDNF‐antisense is reported to be a discordant regulator of BDNF protein expression, such that, when BDNF‐antisense levels increase, BDNF protein expression decreases (Xu et al., 2022). A similar role was suggested for FGF‐antisense (FGF‐AS) in the regulation of FGF2 expression based on initial in vitro studies (Baguma‐Nibasheka et al., 2007, 2012; Li & Murphy, 2000; MacFarlane et al., 2010); however, several other in vitro studies failed to detect an interaction between FGF‐AS and FGF2 expression levels (Asa et al., 2001; Baguma‐Nibasheka et al., 2005, 2012; MacFarlane et al., 2010).…”