Chronic Regulation of miR-124-3p in the Perilesional Cortex after Experimental and Human TBI.
Niina VuokilaEleonora AronicaAnatoly KorotkovErwin Alexander van VlietSalma NuzhatNoora PuhakkaAsla PitkänenPublished in: International journal of molecular sciences (2020)
Traumatic brain injury (TBI) dysregulates microRNAs, which are the master regulators of gene expression. Here we investigated the changes in a brain-enriched miR-124-3p, which is known to associate with major post-injury pathologies, such as neuroinflammation. RT-qPCR of the rat tissue sampled at 7 d and 3 months in the perilesional cortex adjacent to the necrotic lesion core (aPeCx) revealed downregulation of miR-124-3p at 7 d (fold-change (FC) 0.13, p < 0.05 compared with control) and 3 months (FC 0.40, p < 0.05) post-TBI. In situ hybridization confirmed the downregulation of miR-124-3p at 7 d and 3 months post-TBI in the aPeCx (both p < 0.01). RT-qPCR confirmed the upregulation of the miR-124-3p target Stat3 in the aPeCx at 7 d post-TBI (7-fold, p < 0.05). mRNA-Seq revealed 312 downregulated and 311 upregulated miR-124 targets (p < 0.05). To investigate whether experimental findings translated to humans, we performed in situ hybridization of miR-124-3p in temporal lobe autopsy samples of TBI patients. Our data revealed downregulation of miR-124-3p in individual neurons of cortical layer III. These findings indicate a persistent downregulation of miR-124-3p in the perilesional cortex that might contribute to post-injury neurodegeneration and inflammation.
Keyphrases
- traumatic brain injury
- cell proliferation
- severe traumatic brain injury
- gene expression
- single cell
- signaling pathway
- functional connectivity
- mild traumatic brain injury
- end stage renal disease
- oxidative stress
- ejection fraction
- newly diagnosed
- long non coding rna
- peritoneal dialysis
- electronic health record
- brain injury
- poor prognosis
- prognostic factors
- deep learning
- dna methylation
- blood brain barrier
- spinal cord injury
- lipopolysaccharide induced
- long noncoding rna
- binding protein
- subarachnoid hemorrhage