Transcriptional changes after controlled cortical impact in mice
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PROVIDER: PRJNA1011231 | ENA |
REPOSITORIES: ENA
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Project description:Many extracellular matrix (ECM) changes occur in the brain after traumatic brain injury. This work sought to understand the dynamics of ECM modifications after TBI by comparing RNA transcription between ipsilateral and contralateral brain regions. Mice underwent controlled cortical impact (with a 2mm depth) using a pneumatic impactor. Seven days later, brain tissue was harvested from the site of injury and from the corresponding contralateral cortex. Microarrays were used to measure gene expression to compare these tissues.
2024-08-30 | GSE242025 | GEO
Project description:Glutamate-induced transcriptional changes in embryonic mouse cortical neurons [GRO-seq]
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Project description:Neuroprotective potential of intranasally delivered L-myc immortalized human neural stem cells in female rats after a controlled cortical impact injury
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Project description:Efficacious stem cell-based therapies for traumatic brain injury (TBI) depend on successful delivery, migration, and engraftment of stem cells to induce neuroprotection. L-myc expressing human neural stem cells (LMNSC008) demonstrate an inherent tropism to injury sites after intranasal (IN) administration. We hypothesize that IN delivered LMNSC008 cells migrate to primary and secondary injury sites and modulate biomarkers associated with neuroprotection and tissue regeneration. To test this, immunocompetent adult female rats received a controlled cortical impact injury (CCI) or sham surgery. LMNSC008 cells or a vehicle (VEH) were administered IN on postoperative days 7, 9, 11, 13, 15, and 17. The distribution and migration of eGFP-expressing LMNSC008 cells were quantified over 1 mm-thick optically cleared (CLARITY) coronal brain sections from TBI and SHAM controls. NSC migration was observed along white matter tracts projecting toward the hippocampus and regions of TBI. ELISA and Nanostring assays revealed a shift in tissue gene expression in LMNSC008 treated rats relative to controls. LMNSC008 treatment reduced expression of genes and pathways involved in inflammatory response, microglial function, and various cytokines and receptors. The data demonstrate a robust proof-of-concept for LMNSC008 therapy for TBI and provides a strong rationale for IN delivery for translation in TBI patients. NanoString RNAseq sample preparation and data acquisition
2024-02-29 | GSE242031 | GEO
Project description:Traumatic brain injury (TBI) causes transient increases and subsequent decreases in brain glucose utilization. The underlying molecular pathways are orchestrated processes and poorly understood. In the current study, we determined temporal changes in cortical and hippocampal expression of genes important for brain glucose/lactate metabolism and the effect of a known neuroprotective drug telmisartan on the expression of these genes after experimental TBI. Adult male C57BL/6J mice (n?=?6/group) underwent sham or unilateral controlled cortical impact (CCI) injury. Their ipsilateral and contralateral cortex and hippocampus were collected 6?h, 1, 3, 7, 14, 21, and 28?days after injury. Expressions of several genes important for brain glucose utilization were determined by qRT-PCR. In results, (1) mRNA levels of three key enzymes in glucose metabolism [hexo kinase (HK) 1, pyruvate kinase, and pyruvate dehydrogenase (PDH)] were all increased 6?h after injury in the contralateral cortex, followed by decreases at subsequent times in the ipsilateral cortex and hippocampus; (2) capillary glucose transporter Glut-1 mRNA increased, while neuronal glucose transporter Glut-3 mRNA decreased, at various times in the ipsilateral cortex and hippocampus; (3) astrocyte lactate transporter MCT-1 mRNA increased, whereas neuronal lactate transporter MCT-2 mRNA decreased in the ipsilateral cortex and hippocampus; (4) HK2 (an isoform of hexokinase) expression increased at all time points in the ipsilateral cortex and hippocampus. GPR81 (lactate receptor) mRNA increased at various time points in the ipsilateral cortex and hippocampus. These temporal alterations in gene expression corresponded closely to the patterns of impaired brain glucose utilization reported in both TBI patients and experimental TBI rodents. The observed changes in hippocampal gene expression were delayed and prolonged, when compared with those in the cortex. The patterns of alterations were specific to different brain regions and exhibited different recovery periods following TBI. Oral administration of telmisartan (1?mg/kg, for 7?days, n?=?10 per group) ameliorated cortical or hippocampal mRNA for Glut-1/3, MCT-1/2 and PDH in CCI mice. These data provide molecular evidence for dynamic alteration of multiple critical factors in brain glucose metabolism post-TBI and can inform further research for treating brain metabolic disorders post-TBI.
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Project description:Developmental neuron death plays a pivotal role in refining organization and wiring during neocortex formation. Aberrant regulation of this process results in neurodevelopmental disorders including impaired learning and memory. Underlying molecular pathways are incompletely determined. Loss of Bcl11a in cortical projection neurons induces pronounced cell death in upper-layer cortical projection neurons during postnatal corticogenesis. We used this genetic model to explore genetic mechanisms by which developmental neuron death is controlled. Unexpectedly, we found Bcl6, previously shown to be involved in transition of cortical neurons from progenitor to postmitotic differentiation state to provide a major check point regulating neuron survival during late cortical development. We show that Bcl11a is a direct transcriptional regulator of Bcl6. Deletion of Bcl6 exerts death of cortical projection neurons. In turn, reintroduction of Bcl6 into Bcl11a mutants prevents induction of cell death in these neurons. Together, our data identify a novel Bcl11a/Bcl6-dependent molecular pathway in regulation of developmental cell death during corticogenesis.
2022-06-24 | GSE185288 | GEO
Project description:Developmental neuron death plays a pivotal role in refining organization and wiring during neocortex formation. Aberrant regulation of this process results in neurodevelopmental disorders including impaired learning and memory. Underlying molecular pathways are incompletely determined. Loss of Bcl11a in cortical projection neurons induces pronounced cell death in upper-layer cortical projection neurons during postnatal corticogenesis. We used this genetic model to explore genetic mechanisms by which developmental neuron death is controlled. Unexpectedly, we found Bcl6, previously shown to be involved in transition of cortical neurons from progenitor to postmitotic differentiation state to provide a major check point regulating neuron survival during late cortical development. We show that Bcl11a is a direct transcriptional regulator of Bcl6. Deletion of Bcl6 exerts death of cortical projection neurons. In turn, reintroduction of Bcl6 into Bcl11a mutants prevents induction of cell death in these neurons. Together, our data identify a novel Bcl11a/Bcl6-dependent molecular pathway in regulation of developmental cell death during corticogenesis.
2022-06-24 | GSE185287 | GEO
Project description:Astrocytes are implicated in neuronal development, particularly excitatory synaptogenesis, but their genome-wide impact is unclear. Using cell-type specific RNA-seq we show that cortical astrocytes induce widespread transcriptomic changes in developing cortical neurons. Rat cortical neurons were maintained in the presence or absence of mouse astrocytes, RNA-seq performed, and mixed-species RNA-seq reads sorted according to species. Cultures were also treated with TTX to abolish neuronal firing activity, to investigate the effects of the presence or absence activity-dependent signalling.
2024-05-14 | E-MTAB-14070 | biostudies-arrayexpress
Project description:Astrocytes are implicated in neuronal development, particularly excitatory synaptogenesis, but their genome-wide impact is unclear. Using cell-type specific ChIP-seq we show that cortical astrocytes induce widespread changes in developing cortical neurons in histone marks associated with active open chromatin and repressed/condensed chromatin. Rat cortical neurons were maintained in the presence or absence of mouse astrocytes, ChIP-seq performed, and mixed-species ChIP-seq reads sorted according to species.
2024-05-16 | E-MTAB-14081 | biostudies-arrayexpress
Project description:Glutamate is a major excitatory neurotransmitter in the nervous system. Increased and persistent release of glutamate is toxic to neurons and this excitotoxicity is a hallmark of several neurodegenerative diseases. Here, we use GRO-seq to screen for the acute transcriptional changes induced by glutamate exposure on embryonic mouse cortical neurons to reveal downstream molecules which could participate in glutamate-induced toxicity. We show that several miRNA genes, such as miR-21, have altered expression upon glutamate exposure.
2023-01-03 | GSE215210 | GEO