Drug effects on hippocampal microRNA profiles after traumatic brain injury
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE59647 | GEO | 2015/01/08
SECONDARY ACCESSION(S): PRJNA255854
REPOSITORIES: GEO
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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-01-08 | E-GEOD-59647 | biostudies-arrayexpress
Project description:Drug effects on hippocampal microRNA profiles after traumatic brain injury
| PRJNA255854 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-06-14 | E-GEOD-58485 | biostudies-arrayexpress
Project description:Concussion is a heterogeneous injury that relies predominantly on subjective symptom reports for patient assessment and treatment. Developing an objective, biological test could aid phenotypic categorization of concussion patients, leading to advances in personalized treatment. This prospective multi-center study employed saliva micro-ribonucleic acid (miRNA) levels to stratify 251 individuals with concussion into biological subgroups. Using miRNA biological clusters, our objective was to assess for differences in medical/demographic characteristics, symptoms, and functional measures of balance and cognition. The miRNAs that best defined each cluster were used to identify physiological pathways that characterized each cluster. The 251 participants (mean age: 18 ± 7 years; 57% male) were optimally grouped into 10 clusters based on 22 miRNA levels. The clusters differed in age (χ2 = 19.1, p = 0.024), days post-injury at the time of saliva collection (χ2 = 22.6; p = 0.007), and number of prior concussions (χ2 = 17.6, p = 0.040). The clusters also differed in symptom reports for fatigue (χ2 = 17.7; p = 0.039), confusion (χ2 = 22.3; p = 0.008), difficulty remembering (χ2 = 22.0; p = 0.009), and trouble falling asleep (χ2 = 17.2; p = 0.046), but not objective balance or cognitive performance (p > 0.05). The miRNAs that defined concussion clusters regulate 16 physiological pathways, including adrenergic signaling, estrogen signaling, fatty acid metabolism, GABAergic signaling, synaptic vesicle cycling, and transforming growth factor (TGF)-β signaling. These results show that saliva miRNA levels may stratify individuals with concussion based on underlying biological perturbations that are relevant to both symptomology and pharmacological targets. If validated in a larger cohort, miRNA assessment could aid individualized, biology-driven concussion treatment.
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Project description:This SuperSeries is composed of the SubSeries listed below.
2017-02-25 | GSE86615 | GEO
Project description:Traumatic brain injury (TBI) triggers endoplasmic reticulum (ER) stress and impairs autophagic clearance of damaged organelles and toxic macromolecules. In this study, we investigated the effects of the post-TBI administration of docosahexaenoic acid (DHA) on improving hippocampal autophagy flux and cognitive functions of rats. TBI was induced by cortical contusion injury in Sprague-Dawley rats, which received DHA (16 mg/kg in DMSO, intraperitoneal administration) or vehicle DMSO (1 ml/kg) with an initial dose within 15 min after the injury, followed by a daily dose for 3 or 7 days. First, RT-qPCR reveals that TBI induced a significant elevation in expression of autophagy-related genes in the hippocampus, including SQSTM1/p62 (sequestosome 1), lysosomal-associated membrane proteins 1 and 2 (Lamp1 and Lamp2), and cathepsin D (Ctsd). Upregulation of the corresponding autophagy-related proteins was detected by immunoblotting and immunostaining. In contrast, the DHA-treated rats did not exhibit the TBI-induced autophagy biogenesis and showed restored CTSD protein expression and activity. T2-weighted images and diffusion tensor imaging (DTI) of ex vivo brains showed that DHA reduced both gray matter and white matter damages in cortical and hippocampal tissues. DHA-treated animals performed better than the vehicle control group on the Morris water maze test. Taken together, these findings suggest that TBI triggers sustained stimulation of autophagy biogenesis, autophagy flux, and lysosomal functions in the hippocampus. Swift post-injury DHA administration restores hippocampal lysosomal biogenesis and function, demonstrating its therapeutic potential.
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2017-03-08 | GSE64986 | GEO
Project description:The underlying molecular mechanisms of how dysregulated microRNAs (miRNAs) cause neurodegeneration after traumatic brain injury (TBI) remain elusive. Here we analyzed the biological roles of approximately 600 genes - we previously found these dysregulated in dying and surviving rat hippocampal neurons - that are targeted by ten TBI-altered miRNAs. Bioinformatic analysis suggests that neurodegeneration results from a global miRNA-mediated suppression of genes essential for maintaining proteostasis; many are hub genes - involved in RNA processing, cytoskeletal metabolism, intracellular trafficking, cell cycle progression, repair/maintenance, bioenergetics and cell-cell signaling - whose disrupted expression is linked to human disease. Notably, dysregulation of these essential genes would significantly impair synaptic function and functional brain connectivity. In surviving neurons, upregulated miRNA target genes are co-regulated members of prosurvival pathways associated with cellular regeneration, neural plasticity, and development. This study captures the diversity of miRNA-regulated genes that may be essential for cell repair and survival responses after TBI.
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Project description:This SuperSeries is composed of the SubSeries listed below.
2022-12-22 | GSE206941 | GEO
Project description:Time dependent-profiles in the gene expression level following lateral moderate fluid percussion injury in the rat brain We used microarray to elucidate relationship between the alteration of gene expression levels and the progression of brain damages following traumatic brain injury. To examine the levels of gene expression in the early phase of traumatic brain injury, we analyzed the gene expression at 3, 6, 12, and 48 h after trauma using the lateral moderate fluid percussion TBI model. The ratios of the gene expression level were compared between chips corresponding to the 3, 6 and 12 h fluid percussion groups and the sham group chips. On the other hand, the rations of gene expression level after 48 h FPI were compared with 48 h sham chip, because the gene expression levels of 48 h sham chip were distinct from sham group chips (3, 6 and 12 h) in the cluster and principal components analyses.
2010-12-07 | E-GEOD-24047 | biostudies-arrayexpress