Transcriptional screen in the target region of sprouting hindlimb corticospinal fibers after thoracic spinal cord injury in rats
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ABSTRACT:
PROVIDER: PRJNA432265 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6655780.fastq.gz | Fastqsanger.gz | |||
| SRR6655790.fastq.gz | Fastqsanger.gz | |||
| SRR6655800.fastq.gz | Fastqsanger.gz | |||
| SRR6655781.fastq.gz | Fastqsanger.gz | |||
| SRR6655791.fastq.gz | Fastqsanger.gz |
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Project description:Depending on the severity of a CNS injury, in humans as well as in experimental animal models certain degrees of functional recovery are observed. Rodent studies have provided much evidence for underlying anatomical changes involving neurite outgrowth of both spared and axotomized fiber tracts, also referred to as sprouting. Following a thoracic spinal cord injury (SCI) in adult rats, axotomized fibers of the hindlimb corticospinal tract (CST) were found to sprout into the cervical spinal cord at different rostrocaudal levels. Anterograde tracings showed that these new collaterals of motor cortical hindlimb fibers project into the intermediate laminae of the cervical grey matter, particularly pronounced at the level of cervical segment three (C3). The molecular cues which induce the growth and guide these sprouts of hindlimb CST fibers are unknown. We hypothesize that sectreted factors and guidance and adhesion molecules are specifically expressed in the intermediate laminae of the cervical spinal cord to direct and target the ingrowth of the sprouting hindlimb CST fibers. To test our hypothesis the transcription profile of the target region of sprouts was investigated with RNA sequencing of total RNA extracted from the intermediate laminae (IV-VII) of the spinal gray matter at cervical level C3. Four major comparisons were performed, which were then again compared to each other. The first comparison was between samples of animals with an SCI sacrificed at four different time points after injury (1, 3, 6, 12 weeks after injury). The second and third comparison was between samples of rats with a SCI compared to their sham controls sacrificed at the same time point after surgery (1 week or 12 weeks respectively). The fourth comparison was between samples from animals of the two control groups, rats with a sham surgery which were either sacrificed at one or at twelve weeks after injury. We found that most changes in gene expression ocurred at one week after SCI and least changes occured at twelve weeks after SCI, suggesting that the largest effects on a global level of gene expression occur during early time points after injury. Interestingly, also we also found changes in gene expression when comparing the samples from the two control groups, which suggests that sham surgery consisting of a laminectomy is sufficient to induce transcriptional changes in the spinal cord. This is the first study to provide insight into transcriptional changes in the target region of sprouts investigating the role of the cervical spinal cord (target region) for sprouting of hindlimb CST fibers.
2021-01-31 | GSE109902 | GEO
Project description:B-RAF activation in mature corticospinal neurons upregulated a discrete set of transcription factors overlapping with a set induced early in axotomized zebrafish retina ganglion cells which can fully regenerate their axons. Conditional genetic activation of B-RAF promoted robust regeneration and sprouting of corticospinal tract axons after experimental spinal cord injury. Newly sprouting axon collaterals formed synaptic connections, correlating with recovery of skilled motor function. We also found that non-invasive suprathreshold high-frequency repetitive transcranial magnetic stimulation activates the RAF effector MEK and promotes regeneration and sprouting of corticospinal tract axons, dependent on MEK signaling. Our findings demonstrate a central role of neuron-intrinsic RAF–MEK signaling in enhancing the growth capacity of mature corticospinal neurons and propose transcranial magnetic stimulation as a potential therapy for spinal cord injury.
2022-12-31 | GSE201350 | GEO
Project description:In response to cortical stroke and unilateral corticospinal tract degeneration, compensatory sprouting of spared corticospinal fibers is associated with recovery of skilled movement in rodents. To date, little is known about the molecular mechanisms orchestrating this spontaneous rewiring. In this study, we provide insights into the molecular changes in the spinal cord tissue after large ischemic cortical injury in adult female mice, with a focus on factors that might influence the re-innervation process by contralesional corticospinal neurons. We mapped the area of cervical grey matter re-innervation by sprouting contralesional corticospinal axons after unilateral photothrombotic stroke of the motor cortex in mice using anterograde tracing. The mRNA profile of this re-innervation area was analyzed using whole-genome sequencing to identify differentially expressed genes at selected time points during the recovery process. Bioinformatic analysis revealed two phases of processes: Early after stroke (4-7 days post injury), the spinal transcriptome is characterized by inflammatory processes, including phagocytic processes as well as complement cascade activation. Microglia are specifically activated in the denervated corticospinal projection fields in this early phase. In a later phase (28-42 days post injury), biological processes include tissue repair pathways with up-regulated genes related to neurite outgrowth. Thus, the stroke-denervated spinal grey matter, in particular its intermediate laminae, represents a growth-promoting environment for sprouting corticospinal fibers originating from the contralesional motor cortex. This data set provides a solid starting point for future studies addressing key elements of the post-stroke recovery process, with the goal to improve neuroregenerative treatment options for stroke patients.
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2020-01-21 | GSE126957 | GEO
Project description:Activation of MAP2K signaling by genetic engineering or HF-rTMS promotes corticospinal axon sprouting and functional regeneration
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Project description:Molecular mechanisms over differentiation and differential axonal targeting of distinct neuron subtypes in the cerebral cortex are beginning to be elucidated. These studies have focused on controls that specifically distinguish one subtype of neocortical projection neurons, e.g. corticospinal motor neurons (CSMN), from closely related corticothalamic projection neurons (CThPN) or intracortical callosal projection neurons (CPN). CSMN are located in layer V of the neocortex and make synaptic connections to motor output circuitry in the spinal cord and brainstem. CSMN axons form the corticospinal tract (CST), which is the major motor output pathway from the motor cortex and critically controls voluntary movement. CSMN somatotopically and precisely target specific segments along the rostrocaudal axis of the spinal cord, the molecular basis for which remains unknown. We used microarrays to examine gene expression differences between two CSMN subpopulations that target different levels of the spinal cord - CSMN-C (which extend axons to the brainstem and cervical spinal cord) and CSMN-L (which preferrrentially extend axons to the thoracic and lumbar spinal cord). We compared CSMN-C vs CSMN-L gene expression at 3 critical developmental time points (previously described in Arlotta et a., 2005)
2018-12-31 | GSE77311 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE24440: Sprouting transcriptome in cortical neurons: young GSE24441: Sprouting transcriptome in cortical neurons: aged Refer to individual Series
2010-11-15 | E-GEOD-24442 | biostudies-arrayexpress
Project description:Dormant/sprouting bud or eye tissue was collected from field grown Russet Burbank tubers using melon baler. These tubers after harvest washed with 5% Clorox, dried and stored at room temperature and allowed to sprout. Tissue samples were collected from dormant and sprouting eye at different physiological stages (based on length of the sprout) of sprouting. RNA was extracted using a hot phenol method and treated with DNAse. RNA extracted from different stages of sprouting potato tubers was used as query samples. RNA collected from non-sprouting eyes of potato tubers was used as reference samples Information on RNA samples. Plant species: S. tuberosum CV Russet Burbank. Tissue harvested: Tissue was harvested from the dormant/sprouting bud/eye using ½ inch melon baler. Time points: Dormant eyes –Stage 1 Initiating buds/sprouts – Stage 2 Sprouts (1/8 inch) – Stage 3 Sprouts (1/4 inch) – Stage 4 Sprout callus (1/4 inch) – Stage 5 Sprouts (1/2 inch) – Stage 6. Growth conditions: Field grown. Replicate information: Biological replicates; A, B and C Keywords: Direct comparison
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Project description:Analysis of effect of hindlimb suspension and reloading on C57Bl/6 mouse soleus muscle. Experimental groups examined: -Control mice, 14 days -Hindlimb suspension for 7 days -Hindlimb suspension for 7 days, and subsequent reloading for 1 day -Hindlimb suspension for 7 days, and subsequent reloading for 7 days
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