Dexmedetomidine had neuroprotective effects on hippocampal neuronal cells via targeting lncRNA SHNG16 mediated microRNA-10b-5p/BDNF axis

Abstract

Dexmedetomidine (DEX), a highly selective alpha2 adrenergic receptor agonist, is a commonly used anesthetic drug in surgical procedures. Previous studies have indicated that DEX exerts neuroprotective effects while the detailed mechanism has not been fully elucidated. Here, we aim to study the role of lncRNA SHNG16 in DEX-induced brain protection and its underlying molecular mechanism. The rats underwent middle cerebral artery occlusion (MCAO) surgery and oxygen-glucose deprivation (OGD)-treated HT22 hippocampal neurons were treated with DEX, respectively. CCK8 was used to evaluate cell viability. sh-SHNG16 as well as miR-10b-5p mimics were transfected into hippocampal neurons to further explore the bio-function of SNHG16 and miR-10b-5p in vitro. Furthermore, the interactions between SHNG16 and miR-10b-5p, miR-10b-5p and BDNF gene were confirmed by dual-luciferase report assay. Our data revealed that DEX attenuated neurological damage of the MCAO rats and also increased the cell viability of the neurons significantly. Besides, expression of SHNG16 and BDNF were both downregulated while miR-10b-5p was upregulated in MCAO brain tissues or OGD treated neurons. DEX inhibited miR-10b-5p expression but increased SHNG16 and BDNF levels with a dosage effect. After transfection with sh-SHNG16 or miR-10b-5p mimics, the expression of BDNF protein was downregulated, accompanied with decreased neuron viability. Dual-luciferase assay showed that SHNG16 targeted on miR-10b-5p, which also could bind directly to the 3′-UTR sites of BDNF and negatively regulate its expression. In conclusion, DEX exerts neuroprotective in ischemic stroke via improving neuron damage, the underlying mechanism may be upregulating SHNG16 and BDNF via sponging miR-10b-5p.

Factors affecting successful use of intranasal dexmedetomidine: a cohort study from a national paediatrics tertiary centre

“…With rising concern about ICU delirium and neurotoxicity effects of various sedatives on the developing brain, dexmedetomidine has become the preferred choice of sedative in the ICU, given its reported neuroprotective effect (15)(16)(17)(18)(19)(20)(21)(22). This is in contrast to procedural sedation where the use of dexmedetomidine is not routine.…”

Dexmedetomidine improves oxygen-glucose deprivation/reoxygenation (OGD/R) -induced neurological injury through regulating SNHG11/miR-324-3p/VEGFA axis

“…Increasing evidence illustrates that Dex possesses neuroprotective effects in nervous system diseases [11][12][13]. Herein, we further explored the effects of Dex on IS-induced neuronal damage in vitro and in vivo.…”

Dexmedetomidine does not compromise neuronal viability, synaptic connectivity, learning and memory in a rodent model

“…It would therefore appear that under certain experimental conditions DEX may induce neurotoxicity in brain slices and these subsequent effects may involve a variety of signalling pathways. However, in many other instances, DEX appears not only to be non-neurotoxic but also neuroprotective against the toxicity induced by other anesthetic agents such as sevoflurane, propofol or ketamine 22,64,65 . Previous studies have shown a number of anesthetic agents affect synaptic structures and function 33,66,67 ; however, similar conclusive evidence for DEX is missing.…”