ATAC-Seq Reveals the Impact of Mild Traumatic Brain Injury on the Hippocampus
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE292126 | GEO | 2025/12/11
REPOSITORIES: GEO
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Project description:To elucidate molecular features of the cells of Hippocampus, their progeny at each differentiation stage, and surrounding cells in hippocampus undercontrolled cortical impact (CCI) conditions, >15000 cells were profiled from matched hippocampus of 3 mice that had received CCI and 3 sham-operated controls.Cell type specific gene expression responding to (mild traumatic brain injury, mTBI) were revealed, some of which were closely associated with pathogenesis post-injury. Furthermore, the diverse cell to cell interaction networks uncovered an array of cellular processes under mTBI. Our gene expression atlas provides extensive resources for future researches regarding mTBI induced pathogenesis, its therapeutic interventions or diagnostic tests.
2025-12-11 | GSE292715 | GEO
Project description:Purpose: High throughput small RNA-Seq analysis from circulating biofluids is crucial in driving the discovery of non-invasive miRNA biomarkers for TBI. In this study, we focused our analysis on acute post-TBI alterations in plasma miRNA profiles in adult, male Sprague-Dawley rats. We compared the plasma miRNA profiles from naive, sham-operated controls and rats with mild and severe TBI. The aim was to identify a miRNA signature that would distinguish the rats with mTBI from the naive and sham-operated controls. Next, we compared the rats with mild and severe TBIs to investigate if a dose-dependent increase would occur in the plasma miRNA levels with corresponding increase in injury severities. Finally, we analysed if the sham surgery itself results in alterations in circulating miRNA profiles, by comparing the naive and sham-operated controls. Methods: TBI was induced with the lateral fluid percussion injury (FPI) model. Tail-vein plasma was collected at 2 days post-TBI from 31 adult male, Sprague-Dawley rats (5 naive, 8 sham-operated controls, 10 mTBI and 8 sTBI) under inhalation of isoflurane anesthesia. Small RNA-Seq was performed from plasma samples of a subset of 20 rats (5 cases each from naive, sham-operated controls, mTBI and sTBI groups). For each case, RNA was isolated from 200 µL plasma using the miRNeasy serum/plasma kit. The extracted RNA was subjected to qPCR-based quality control (QC). Small RNA library preparation was performed with the QIASeq miRNA library kit for Illumina NGS systems. Single-end sequencing of 75 bp reads was performed at a depth of 12M, with one sample/lane in the Illumina NextSeq 550. One naive plasma sample failed at the library preparation step. Hence, small RNA-Seq was succesful for 19/20 cases. The raw fastq files obtained from small RNA-Seq were first manually inspected with FastQC (v0.11.3) to check the overall quality of the sequencing data. For primary quantification of read counts, the fastq files were then uploaded to the Qiagen Geneglobe Data analysis center (DAC), a freely available web resource to analyze data from Qiagen’s QIASeq NGS library kits (https://geneglobe.qiagen.com/in/analyze/). Mapping was performed in the DAC portal with bowtie, using the rat reference genome RGSC Rnor_6.0. Annotation of miRNAs was performed with miRBase v21. Following primary quantification, differential expression analysis for miRNAs was performed with DESeq2 (v1.22.2) in R environment (v3.5.3). Logistic regression (LR) with feature selection utilizing nested leave-one-out cross-validation was also performed to identify miRNAs (“features”) contributing most to groupwise differences (differences between naïve, sham, mTBI, sTBI, sTBI + mTBI and naïve + sham). Results: A total of 748 miRNAs were detected across all samples, out of which 723 (97%) were expressed in all the four groups (naive, sham-operated, mTBI and sTBI). Based on the differential expression and logistic regression analyses, we identified five miRNA candidates that contributed most to the seperation between the mTBI and naive groups: rno-miR-9a-3p, rno-miR-153-3p, rno-miR-15a-3p, rno-miR-136-3p and rno-miR-434-3p. We validated the small RNA-Seq data for these miRNA candidates with miRCURY reverse transcriptase quantitative PCR (RT-qPCR). We could succesfully validate elevated levels of miR-9a-3p, miR-136-3p and miR-434-3p in the mTBI group in comparison to naive. When analysed from the whole cohort, the elevated levels of these miRNAs were consistently observed in the mTBI group compared to the naive, both with RT-qPCR and droplet digital PCR (ddPCR). Further, all the three miRNAs revealed elevated plasma levels in the sTBI group in comparison to the mTBI. Conclusions: Elevated plasma miRNA signature of miR-9a-3p, miR-136-3p and miR-434-3p distinguishes rats with mTBI from the naive, in the lateral FPI model of TBI. Further, all these miRNAs exhibit a dose-dependent increase in plasma levels with increase in injury severities.
2021-03-03 | GSE159011 | GEO
Project description:Transcriptional profiling of rat hippocampus 4.5h post intracranial self-stimulation (ICSS) show that this treatment, which improves learning and memory processes in a variety of paradigms of implicit and explicit memory, regulates gene expression of genes related to cAMP-mediated signaling and regulation of synaptic plasticity, among others. Rats were implanted with a monopolar stainless steel electrode aimed at the lateral hypothalamus in the right hemisphere. Hippocampal gene expression was analyzed 4.5h post treatment comparing rats subjected to acute self-stimulation (2500 stimulation trains; ICSS group) with sham-operated rats (with electrode placement but placed in the ICSS without stimulation during 40 min.; Sham group). Two-condition experiment, ICSS and Sham. Every sample consisted of pooled hippocampi ipsilateral to the electrode from three rats. Slices between Bregma levels -2 and -4 were used for dissections of the hippocampi. Common reference design, comparing every condition versus a brain pooled tissue consisting of pooled hippocampal tissue ipsilateral to the electrode of sham-operated (n=3) and stimulated (n=3) rats. Biological replicates: 4 DBS and 4 sham. One replicate per array.
2013-09-03 | E-GEOD-42793 | biostudies-arrayexpress
Project description:Traumatic brain injury (TBI) is a global problem reaching near epidemic numbers that manifests clinically with cognitive problems that decades later may result in dementias like Alzheimer’s disease (AD). Presently, little can be done to prevent ensuing neurological dysfunctions by pharmacological means. Recently, it has become apparent that several CNS diseases share common terminal features of neuronal cell death. The effects of exendin-4 (Ex-4), a neuroprotective agent delivered via a subcutaneous micro-osmotic pump, were examined in the setting of mild TBI (mTBI). Utilizing a model of mTBI, where cognitive disturbances occur over time, animals were subjected to four treatments: sham; Ex-4; mTBI and Ex-4/mTBI. mTBI mice displayed deficits in novel object recognition, while Ex-4/mTBI mice performed similar to sham. Hippocampal gene expression, assessed by gene array methods, showed significant differences with little overlap in co-regulated genes between groups. Importantly, changes in gene expression induced by mTBI, including genes associated with AD were largely prevented by Ex-4. These data suggest a strong beneficial action of Ex-4 in managing secondary events induced by a traumatic brain injury.
2012-10-17 | GSE41345 | GEO
Project description:Transcriptional profiling of rat hippocampus comparing rats subjected to chronic (1 hour daily during 14 days) vetrolateral thalamus stimulation (DBS group) with sham operated rats (with electrode placement but without stimulation) and with naive rats. Three-condition experiment, DBS, sham and naive. Every sample consisted of pooled hippocampi from three rats. Slices between Bregma levels -2 and -4 were used for dissections of the hippocampi. Common reference design, comparing every condition versus a brain pooled tissue consisting of pooled hippocampal, thalamic and cortical brain tissue of the naive (n=4), sham-operated (n=5) and stimulated (n=4) rats. Biological replicates: 4 DBS, 4 sham and 3 naive. One replicate per array. Deep brain stimulation
2011-06-30 | E-GEOD-25860 | biostudies-arrayexpress
Project description:The subventricular zone (SVZ) is a neurogenetic niche that contributes to homeostasis and repair after brain injury. However, effects of mild traumatic brain injury (mTBI) on genomewide gene expression in the SVZ remain largely unexplored. To address this issue, we investigated the single-nucleus transcriptomic profiles of the SVZ after mTBI. 18 distinct clusters were yielded via unsupervised clustering of the transcriptomic profiles. Cell type specific gene expression responding to mTBI were revealed, some of which were closely associated with pathogenesis post-injury. Furthermore, the diverse cell to cell interaction networks uncovered an array of cellular processes under mTBI. Also, we reported novel lineage trajectories and molecular hallmarks that govern the neurogenesis. Our gene expression atlas provides extensive resources for future researches regarding mTBI induced pathogenesis, its therapeutic interventions or diagnostic tests.
2022-06-28 | GSE198074 | GEO
Project description:The cholecystokinin B (2) receptor knockout (Cckbr KO) protects against allodynia induced by chronic constriction injury (CCI). The mechanism of this phenomenon is unknown, but must involve persistent changes in pain modulation and/or inflammatory pathways. We performed a gene expression study in two brain areas (midbrain and medulla) after surgical induction of CCI in Cckbr KO and wild-type (wt) control mice. The patterns of gene expression differences suggest that the immune system is activated in higher brain structures following CCI in the wt mice. The strongest differences include genes related to the MAPK pathway activation and cytokine production. In Cckbr KO mice this expressional pattern was absent. In addition, we found significant elevation of the Toll-like receptor 4 (Tlr4) in the supraspinal structures of the mice with deleted Cckbr compared to wt control mice. This up-regulation is most likely induced by the deletion of Cckbr. We suggest that there is a functional deficiency in the Tlr4 pathway which disables the development of neuropathic pain in Cckbr KO mice. Indeed, real time PCR analysis detected a CCI-induced upregulation of Tlr4 and Il1b expression in the lumbar region of wt but not Cckbr KO mice. Gene expression profiling indicates that elements of the immune response are not activated in Cckbr KO mice following CCI. Our findings suggest that there may be a role for CCK in the regulation of innate immunity. Experiment Overall Design: 32 chips altogether, 4 mutant mice sham-operated, 4 control mice sham-operated, 4 mutant mice CCI-operated, 4 control mice CCI-operated, midbarin and medulla samples from each animals
2008-06-16 | E-GEOD-9594 | biostudies-arrayexpress
Project description:In order to assess the impact of treadmill exercise on traumatic brain injury outcomes, we subjected male and female swiss webster mice to a controlled cortical impact (CCI), followed by 10 days of sedentary, low-, moderate-, or high-intensity treadmill exercise. Outcome measures included neurometabolic function, cognitive recovery, oxidative stress, pathophysiology, and single nuclei RNA sequencing (snRNA seq). The snRNA seq study was conducted on both male and female mice, and included a total of 2 replicates (each was a pool of 2 tissue samples) from each of the following groups: male sham sedentary, male CCI sedentary, male CCI low, male CCI high, female sham sedentary, female CCI sedentary, female CCI low, female CCI high. Our data reveal exercise intensity- and sex-dependent effects of treadmill exercise following injury. Transcriptomic changes were largely limited to the low-intensity exercised CCI males.
2023-08-01 | GSE226072 | GEO
Project description:We aimed to identify molecular signatures of astrocytes isolated from the cortex in sham or CCI injured mice with or without spontaneous recurrent seizures
2024-04-16 | GSE248371 | GEO
Project description:Transcriptional profiling of rat hippocampus 4.5h post intracranial self-stimulation (ICSS) show that this treatment, which improves learning and memory processes in a variety of paradigms of implicit and explicit memory, regulates gene expression of genes related to cAMP-mediated signaling and regulation of synaptic plasticity, among others. Rats were implanted with a monopolar stainless steel electrode aimed at the lateral hypothalamus in the right hemisphere. Hippocampal gene expression was analyzed 4.5h post treatment comparing rats subjected to acute self-stimulation (2500 stimulation trains; ICSS group) with sham-operated rats (with electrode placement but placed in the ICSS without stimulation during 40 min.; Sham group).
2013-09-03 | GSE42793 | GEO