The potential role of non-coding RNAs in the response of the transcriptome to the action of the peptide drug Semax in cerebral ischemia in rats

The use of neuroprotective drugs is a key approach in the treatment of ischemic stroke. Natural peptides, including adrenocorticotropic hormone (ACTH), can serve as the basis for such drugs. The synthetic peptide ACTH(4-7)PGP (Semax) has pronounced nootropic and neuroprotective effects. We previously demonstrated that Semax compensates for changes in gene expression in the rat brain that occur during cerebral ischemia; however, the nature of Semax’s compensatory effect at the transcriptome level remains unclear. We also previously demonstrated that the level of noncoding circular RNAs (circRNAs) significantly changes in the rat brain under ischemic conditions. These circRNAs can act as molecules regulating gene expression by controlling microRNA activity. Under ischemia-reperfusion model conditions in the ipsilateral frontal cortex of rats, containing the penumbra region, we identified genes whose expression is altered by Semax and simultaneously under the control of circRNAs at 24 hours after the onset of middle cerebral artery occlusion. Thus, a possible role of non-coding RNAs in the mechanisms of Semax’s effect on the brain cell transcriptome under ischemic conditions was demonstrated.

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