Activation of MAP2K signaling by genetic engineering or HF-rTMS promotes corticospinal axon sprouting and functional regeneration
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA830919 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18899204_1.fastq.gz | Fastqsanger.gz | |||
| SRR18899204_2.fastq.gz | Fastqsanger.gz | |||
| SRR18899205_1.fastq.gz | Fastqsanger.gz | |||
| SRR18899205_2.fastq.gz | Fastqsanger.gz | |||
| SRR18899206_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
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:Injury to the adult mammalian central nervous system induces compensatory plasticity of spared axons-referred to as collateral axon sprouting-that can facilitate neural recovery. The contribution of reactive astrocytes to axon sprouting remains elusive. Here, we sought to investigate the role of axon degeneration-reactive astrocytes in the regulation of collateral axon sprouting that occurs in the mouse spinal cord after unilateral photothrombotic stroke of the primary motor cortex. We identified astrocytic leucine zipper-bearing kinase (LZK) as a positive regulator of astrocyte reactivity to corticospinal axon degeneration. Remarkably, genetic stimulation of astrocyte reactivity, via LZK overexpression in adult astrocytes, enhanced corticospinal axon sprouting. LZK promoted the production of astrocyte-derived ciliary neurotrophic factor (CNTF) that likely enhanced axon growth in mice with astrocytic LZK overexpression after injury. Our finding that LZK-dependent stimulation of astrocyte reactivity promotes corticospinal axon sprouting highlights the potential of engineering astrocytes to support injury-induced axon plasticity for neural repair.
| S-EPMC9520579 | biostudies-literature
Project description:Functional deficits persist after spinal cord injury (SCI) because axons in the adult mammalian central nervous system (CNS) fail to regenerate. However, modest levels of spontaneous functional recovery are typically observed after trauma, and are thought to be mediated by the plasticity of intact circuits. The mechanisms underlying intact circuit plasticity are not delineated. Here, we characterize the in vivo transcriptome of sprouting intact neurons from ngr1 null mice after partial SCI. We identify the lysophosphatidic acid signaling modulators Lppr1 and Lpar1 as intrinsic axon growth modulators for intact corticospinal motor neurons after adjacent injury. Furthermore, in vivo Lpar1 inhibition or Lppr1 overexpression enhances sprouting of intact corticospinal tract axons and yields greater functional recovery after unilateral brainstem lesion in wild type mice. Thus, the transcriptional profile of injury-induced sprouting of intact neurons reveals targets for therapeutic enhancement of axon growth initiation and new synapse formation.
2017-03-13 | GSE94482 | GEO
Project description:Despite substantial progress in understanding the biology of axon regeneration in the CNS, our ability to promote the regeneration of the clinically important corticospinal tract (CST) after spinal cord injury remains limited. To understand regenerative heterogeneity, we conducted patch-based single cell RNA sequencing on rare regenerating CST neurons at high depth following PTEN and SOCS3 deletion. Supervised classification with Garnett gave rise to a Regenerating Classifier, which can be broadly applied to predict the regenerative potential of diverse neuronal types across developmental stages or after injury. Network analyses highlighted the importance of antioxidant response and mitochondrial biogenesis. Conditional gene deletion validated a role for NFE2L2 (or NRF2), a master regulator of antioxidant response, in CST regeneration. Our data demonstrate a universal transcriptomic signature underlying the regenerative potential of vastly different neuronal populations, and illustrate that deep sequencing of only hundreds of phenotypically identified neurons has the power to advance regenerative biology.
2023-08-08 | GSE205769 | GEO
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:In the present study, we identify transcriptional mechanisms associated with corticospinal regeneration. We took advantage of the ability of NPC grafts to support corticospinal regeneration, together with a genetic mouse model (Glt25d2-GFP-L10a mice, in which a bacterial artificial chromosome (BAC) codes for GFP-tagged polyribosomes in layer 5b cortical neurons) to selectively enrich actively translated mRNA pools from layer Vb cortical projection neurons containing corticospinal neurons (Doyle et al., Cell 2008).
2020-01-21 | GSE126957 | GEO
Project description:After injury to the central nervous system (CNS), both neuron-intrinsic limitations on regenerative responses and inhibitory factors in the injured CNS environment restrict regenerative axon growth. Instances of successful axon regrowth offer opportunities to identify features that differentiate these situations from that of the normal adult CNS. One such opportunity is provided by the kinase inhibitor RO48, which dramatically enhances neurite outgrowth of neurons in vitro and substantially increased contralateral sprouting of corticospinal tract neurons when infused intraventricularly following unilateral pyramidotomy. The authors present here a transcriptomic deconvolution of RO48-associated axon growth, with the goal of identifying transcriptional regulators associated with axon growth in the CNS. Through the use of RNA sequencing (RNA-seq) and transcription factor binding site enrichment analysis, the authors identified a list of transcription factors putatively driving differential gene expression during RO48-induced neurite outgrowth of rat hippocampal neurons in vitro. The 82 transcription factor motifs identified in this way included some with known association to axon growth regulation, such as Jun, Klf4, Myc, Atf4, Stat3, and Nfatc2, and many with no known association to axon growth. A phenotypic loss-of-function screen was carried out to evaluate these transcription factors for their roles in neurite outgrowth; this screen identified several potential outgrowth regulators. Subsequent validation suggests that the Forkhead box (Fox) family transcription factor Foxp2 restricts neurite outgrowth, while FoxO subfamily members Foxo1 and Foxo3a promote neurite outgrowth. The authors’ combined transcriptomic-phenotypic screening strategy therefore allowed identification of novel transcriptional regulators of neurite outgrowth downstream of a multitarget kinase inhibitor.
2023-06-19 | GSE234696 | GEO
Project description:Transcriptional screen in the target region of sprouting hindlimb corticospinal fibers after thoracic spinal cord injury in rats
| PRJNA432265 | ENA
Project description:Transcranial Magnetic Stimulation (TMS) is a noninvasive technique that uses pulsed magnetic fields to affect the physiology of the brain and central nervous system. Repetitive TMS (rTMS) has been used in the study and treatment of neurological conditions including major depression, stroke, epilepsy, schizophrenia, multiple sclerosis, Parkinson’s, and Alzheimer’s disease, as well as other, non-neurological disorders. Among the effects of rTMS, low-frequency protocols (≤ 1Hz) are generally understood to result in cortical inhibition, whereas high-frequency protocols (≥ 3Hz) increase cortical excitability. However, the complex molecular basis of rTMS is largely unexplored. Using three complementary rat models, in vitro, ex vivo, and in vivo, we show complex patterns of hippocampal and neocortical transcriptional response to stimulation in glutamatergic and GABAergic signaling pathways, as well as multiple inflammatory pathways, among others. This broad-based molecular survey helps provide a foundation to tease out the complex molecular mechanisms of the effects of rTMS.
2023-05-30 | GSE230148 | GEO
Project description:Transcranial Magnetic Stimulation (TMS) is a noninvasive technique that uses pulsed magnetic fields to affect the physiology of the brain and central nervous system. Repetitive TMS (rTMS) has been used in the study and treatment of neurological conditions including major depression, stroke, epilepsy, schizophrenia, multiple sclerosis, Parkinson’s, and Alzheimer’s disease, as well as other, non-neurological disorders. Among the effects of rTMS, low-frequency protocols (≤ 1Hz) are generally understood to result in cortical inhibition, whereas high-frequency protocols (≥ 3Hz) increase cortical excitability. However, the complex molecular basis of rTMS is largely unexplored. Using three complementary rat models, in vitro, ex vivo, and in vivo, we show complex patterns of hippocampal and neocortical transcriptional response to stimulation in glutamatergic and GABAergic signaling pathways, as well as multiple inflammatory pathways, among others. This broad-based molecular survey helps provide a foundation to tease out the complex molecular mechanisms of the effects of rTMS.
2023-05-30 | GSE230147 | GEO