MicroRNA-23a-3p improves traumatic brain injury through modulating the neurological apoptosis and inflammation response in mice

Abstract

Secondary brain damage plays an important role in Traumatic brain injury (TBI) and inhibition of this damage has benefit for TBI treatment. However, the pathogenesis of secondary brain damage remains largely unknown. Here, we tried to explore the influence of microRNAs (miRNAs) on neuron apoptosis and inflammatory response after TBI. Firstly, the miRNA expression profiles were analyzed in the cerebral cortex tissues from the TBI mice model (controlled cortical impact) using miRNA microarray. miR-23a-3p (miR-23a) attracted our attention as its suppressive effects on apoptosis and inflammation. The further results showed that miR-23a upregulation improved long-term neurological function, the neuron apoptosis, and inhibited neuroinflammation, whereas knockdown of miR-23a had an opposite result. Using etoposide-induced primary cortical neurons injury model, we found that miR-23a was decreased in this cell model and miR-23a overexpression-suppressed etoposide induced the activity of caspase 3 and the releases of inflammatory mediators in primary cortical neurons. Phosphatase and tensin homolog (PTEN), a well-known regulator of the AKT/mTOR pathway, was found to be a direct target of miR-23a in the primary cortical neurons. Most importantly, it was found that miR-23a overexpression reactivated the AKT/ mTOR pathway in TBI mice model, as demonstrated by the upregulation of phosphorylated (p-) AKT and p-mTOR. Taken together, these data indicate that miR-23a may serve as a therapeutic target for the treatment of TBI.

MicroRNA-23a reduces lipopolysaccharide-induced cellular apoptosis and inflammatory cytokine production through Rho-associated kinase 1/sirtuin-1/nuclear factor-kappa B crosstalk

“…[ 26 ] Furthermore, the anti-inflammatory functions of miR-23a have been observed in articular chondrocytes [ 27 ] and neurons of rats presenting brain injury. [ 28 ] Similarly, silencing of lncRNA MALAT1, a miR-23a sponge, was reported to promote cell growth and repress inflammatory response in septic mice, indicating the protective role of miR-23a against sepsis-induced cell damage, [ 12 ] which was substantiated in the current study. Moreover, we observed that miR-23a overexpression inhibited apoptosis in LPS-treated cells; the decreased caspase-3 activity induced by the miR-23a mimic additionally suggested the anti-apoptotic role of miR-23a from a molecular perspective.…”

microRNA‐9‐5p alleviates blood–brain barrier damage and neuroinflammation after traumatic brain injury

“…Phosphatase and tensin homolog (PTEN), a well-known regulator of the AKT/mTOR pathway, was found to be a direct target of miRNA-23a-3p. A recent study found that the level of miRNA-23a-3p was decreased after TBI and up-regulation of miRNA-23a-3p inhibited cortical neuron apoptosis and improved the neural function (Li et al, 2020). MiRNA-9 is highly expressed in the central nervous system and plays an important role in the differentiation of neural stem cells (Hu et al, 2014;Topol et al, 2016).…”

Downregulation of microRNA-9-5p promotes synaptic remodeling in the chronic phase after traumatic brain injury

“…PTEN, which is an important regulatory protein of the AKT/mTOR pathway, is a direct target of miR-23a-3p. Previous studies have reported that upregulation of miR-23a-3p can inhibit cortical neuron apoptosis and improve neurological function by regulating the AKT/mTOR pathway 18 . miRNA-9 is highly expressed in the central nervous system and plays an important role in the differentiation and synaptic formation of neural stem cells 19 .…”