MicroRNA sequencing of rat hippocampus and human biofluids identifies acute, chronic, focal and diffuse traumatic brain injuries

Abstract

age-matched control serum. In these exploratory studies with rat and human tissues, we tested three hypotheses, 1) miRNA-seq profiles would identify TBI at all acute and chronic post-injury intervals, 2) miRNA-seq profiles would discriminate between focal and diffuse TBI and 3) serum miRNA-seq would reveal potential miRNA markers of neuropsychiatric and neurodegenerative sequelae. Methods Study design. The miRNA-seq and data analyses workflow is shown in Fig. 1A (rat studies) and Fig. 2A (human studies). Detailed methods, including rat surgical procedures, are described in Supplementary Materials and are summarized below. All procedures were done under a protocol (No. 1312056A) approved by the University of Texas Medical Branch at Galveston's Institutional Animal Care and Use Committee. All procedures performed as part of this study were performed in accordance with institutional, state, and U.S. federal guidelines and regulations. In the rat studies, for each post-injury interval, we sequenced four TBI and four sham-control hippocampi, thus 56 rats were used for miRNA-seq analysis. In the human studies, we sequenced 51 serum samples (six acute and six aged controls, 33 acute TBI representing 24, 48, 96 h post-injury, six chronic TBI [2-32 years post-injury]). Demographic characteristics are shown in Table 1. Rat hippocampus and serum isolation and PCR array analysis. Total RNA from rat hippocampal tissue was extracted and purified using Ribopure (Ambion) as in Boone and Weisz et al. 9. Serum from rats subjected to FPI and CCI was used for miRNA isolation and PCR array analysis as described in Supplementary Methods.

Scopolamine promotes neuroinflammation and delirium-like neuropsychiatric disorder in mice

“…We have selected hippocampus as it is the specific brain region critical for learning and memory process, and known to have significant association with the neuropsychiatric behavioral changes by various studies. Other previous studies had also extracted RNA from hippocampal tissue to examine the RNA changes in neurobehavioral insults and changes in cognition and memory 47 , 48 . After scopolamine treatment, mice showed decreased expression patterns of cholinergic genes ( Chrnb3 , Chrnb4 , Chat , Camk2b , Slc18a3 , Chrm1 ) compared to the vehicle, although statistical significances were lacking.…”

MicroRNA-204-5p reduction in rat hippocampus contributes to stress-induced pathology via targeting RGS12 signaling pathway

“…Differentially expressed miRNAs were then screened from the RNA-sequencing results and a KEEG database analysis was performed. Based on KEEG analysis of miR-204-5p and its downstream predictive target genes and previous literature reports, it is concluded that miR-204-5p is associated with a variety of diseases related to the central nervous system [ 26 ]. Findings from previous reports revealed that miR-204-5p is involved in multiple signaling pathways and results from related studies have shown that miR-204-5p is involved with oxidative stress-related pathways, in specific to the oxidative capacity of mitochondria as demonstrated in vivo [ 27 – 29 ].…”

Identification of key genes and pathways associated with resting mast cells in meningioma

“…However, no evidence of a correlation between hsa-miR-145-5p, or miR-335-3p and meningioma was reported till now. Notwithstanding, miR-145-5p is linked to psychiatric and neurodegenerative disorders [ 46 ]. Further, circPTN can sponge miR-145-5p to promote stemness or proliferation in glioma [ 47 ].…”