RESUMO
Mammals do not possess the ability to spontaneously repair or regenerate damaged retinal tissue. In contrast to teleost fish which are capable of retina regeneration through the action of Müller glia, mammals undergo a process of reactive gliosis and scarring that inhibits replacement of lost neurons. Thus, it is important to discover novel methods for stimulating mammalian Müller glia to dedifferentiate and produce progenitor cells that can replace lost retinal neurons. Inducing an endogenous regenerative pathway mediated by Müller glia would provide an attractive alternative to stem cell injections or gene therapy approaches. Extracellular vesicles (EVs) are now recognized to serve as a novel form of cell-cell communication through the transfer of cargo from donor to recipient cells or by the activation of signaling cascades in recipient cells. EVs have been shown to promote proliferation and regeneration raising the possibility that delivery of EVs could be a viable treatment for visual disorders. Here, we provide protocols to isolate EVs for use in retina regeneration experiments.
Assuntos
Vesículas Extracelulares , Regeneração , Retina , Animais , Vesículas Extracelulares/metabolismo , Retina/metabolismo , Retina/citologia , Retina/fisiologia , Células Ependimogliais/metabolismo , Células Ependimogliais/citologia , Camundongos , Comunicação Celular , Proliferação de Células , Regeneração Nervosa/fisiologiaRESUMO
Various strategies for replacing retinal neurons lost in degenerative diseases are under investigation, including stimulating the endogenous regenerative capacity of Müller Glia (MG) as injury-inducible retinal stem cells. Inherently regenerative species, such as zebrafish, have provided key insights into mechanisms regulating MG dedifferentiation to a stem-like state and the proliferation of MG and MG-derived progenitor cells (MGPCs). Interestingly, promoting MG/MGPC proliferation is not sufficient for regeneration, yet mechanistic studies are often focused on this measure. To fully account for the regenerative process, and facilitate screens for factors regulating cell regeneration, an assay for quantifying cell replacement is required. Accordingly, we adapted an automated reporter-assisted phenotypic screening platform to quantify the pace of cellular regeneration kinetics following selective cell ablation in larval zebrafish. Here, we detail a method for using this approach to identify chemicals and genes that control the rate of retinal cell regeneration following selective retinal cell ablation.
Assuntos
Peixe-Zebra , Animais , Retina/citologia , Retina/metabolismo , Fenótipo , Proliferação de Células , Regeneração , Células Ependimogliais/citologia , Células Ependimogliais/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Cinética , Regeneração Nervosa/fisiologiaRESUMO
ABSTRACT: Peripheral nerve injuries (PNIs) represent a complex clinical challenge, necessitating precise diagnostic approaches for optimal management. Traditional diagnostic methods often fall short in accurately assessing nerve recovery as these methods rely on the completion of nerve reinnervation, which can prolong a patient's treatment. Diffusion tensor imaging (DTI), a noninvasive magnetic resonance imaging (MRI) technique, has emerged as a promising tool in this context. DTI offers unique advantages including the ability to quantify nerve recovery and provide in vivo visualizations of neuronal architecture. Therefore, this review aims to examine and outline DTI techniques and its utility in detecting distal nerve regeneration in both preclinical and clinical settings for peripheral nerve injury.
Assuntos
Imagem de Tensor de Difusão , Regeneração Nervosa , Traumatismos dos Nervos Periféricos , Humanos , Traumatismos dos Nervos Periféricos/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Regeneração Nervosa/fisiologiaRESUMO
The peripheral nervous system consists of ganglia, nerve trunks, plexuses, and nerve endings, that transmit afferent and efferent information. Regeneration after a peripheral nerve damage is sluggish and imperfect. Peripheral nerve injury frequently causes partial or complete loss of motor and sensory function, physical impairment, and neuropathic pain, all of which have a negative impact on patients' quality of life. Because the mechanism of peripheral nerve injury and healing is still unclear, the therapeutic efficacy is limited. As peripheral nerve injury research has processed, an increasing number of studies have revealed that biological scaffolds work in tandem with progenitor cells to repair peripheral nerve injury. Here, we fabricated collagen chitosan nerve conduit bioscaffolds together with collagen and then filled neuroepithelial stem cells (NESCs). Scanning electron microscopy showed that the NESCs grew well on the scaffold surface. Compared to the control group, the NESCs group contained more cells with bigger diameters and myelinated structures around the axons. Our findings indicated that a combination of chitosan-collagen bioscaffold and neural stem cell transplantation can facilitate the functional restoration of peripheral nerve tissue, with promising future applications and research implications.
Assuntos
Quitosana , Colágeno , Regeneração Nervosa , Traumatismos dos Nervos Periféricos , Alicerces Teciduais , Quitosana/química , Regeneração Nervosa/fisiologia , Colágeno/química , Animais , Alicerces Teciduais/química , Traumatismos dos Nervos Periféricos/terapia , Ratos , Células Neuroepiteliais/citologia , Células-Tronco Neurais/citologia , Nervos Periféricos/fisiologia , Nervo Isquiático/fisiologiaRESUMO
The complex interplay between vascular signaling and neurogenesis in the adult brain remains a subject of intense research. By exploiting the unique advantages of the zebrafish model, in particular the persistent activity of neural stem cells (NSCs) and the remarkable ability to repair brain lesions, we investigated the links between NSCs and cerebral blood vessels. In this study, we first examined the gene expression profiles of vascular endothelial growth factors aa and bb (vegfaa and vegfbb), under physiological and regenerative conditions. Employing fluorescence in situ hybridization combined with immunostaining and histology techniques, we demonstrated the widespread expression of vegfaa and vegfbb across the brain, and showed their presence in neurons, microglia/immune cells, endothelial cells and NSCs. At 1 day post-lesion (dpl), both vegfaa and vegfbb were up-regulated in neurons and microglia/peripheral immune cells (macrophages). Analysis of vegf receptors (vegfr) revealed high expression throughout the brain under homeostatic conditions, with vegfr predominantly expressed in neurons and NSCs and to a lower extent in microglia/immune cells and endothelial cells. These findings were further validated by Vegfr3 and Vegfr4 immunostainings, which showed significant expression in neurogenic radial glial cells.Following brain lesion (1 dpl), while vegfr gene expression remained stable, vegfr transcripts were detected in proliferative cells within the injured parenchyma. Collectively, our results provide a first overview of Vegf/Vegfr signaling in the brain and suggest important roles for Vegf in neurogenesis and regenerative processes.
Assuntos
Encéfalo , Neurogênese , Fator A de Crescimento do Endotélio Vascular , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Neurogênese/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Encéfalo/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Células-Tronco Neurais/metabolismo , Fator B de Crescimento do Endotélio Vascular/metabolismo , Fator B de Crescimento do Endotélio Vascular/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Regeneração Nervosa/fisiologiaRESUMO
While the enteric nervous system (ENS) is highly dynamic during development, the extent to which it is capable of repair remains unclear. In this issue of Neuron, Stavely et al.1 show that enteric neurons can reinnervate damaged regions to regain functionality using a glial positioning system (GPS) as their guide.
Assuntos
Sistema Nervoso Entérico , Regeneração Nervosa , Neuroglia , Neuroglia/fisiologia , Sistema Nervoso Entérico/fisiologia , Sistema Nervoso Entérico/citologia , Animais , Regeneração Nervosa/fisiologia , Neuritos/fisiologia , Intestinos/fisiologia , HumanosRESUMO
Nanomedicine is a newer, promising approach to promote neuroprotection, neuroregeneration, and modulation of the blood-brain barrier. This review includes the integration of various nanomaterials in neurological disorders. In addition, gelatin-based hydrogels, which have huge potential due to biocompatibility, maintenance of porosity, and enhanced neural process outgrowth, are reviewed. Chemical modification of these hydrogels, especially with guanidine moieties, has shown improved neuron viability and underscores tailored biomaterial design in neural applications. This review further discusses strategies to modulate the blood-brain barrier-a factor critically associated with the effective delivery of drugs to the central nervous system. These advances bring supportive solutions to the solving of neurological conditions and innovative therapies for their treatment. Nanomedicine, as applied to neuroscience, presents a significant leap forward in new therapeutic strategies that might help raise the treatment and management of neurological disorders to much better levels. Our aim was to summarize the current state-of-knowledge in this field.
Assuntos
Barreira Hematoencefálica , Nanomedicina , Neuroproteção , Humanos , Nanomedicina/métodos , Nanomedicina/tendências , Neuroproteção/fisiologia , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/fisiologia , Fármacos Neuroprotetores/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/terapia , Hidrogéis/uso terapêuticoRESUMO
Objectives: Vitamin B complexes are frequently used in clinical practice for peripheral nerve trauma. However, there is a lack of scientific data on their effectiveness. This study aims to investigate the impact of the vitamin B complex on nerve recovery in a rat model of peripheral nerve paralysis. Materials and Methods: Sixty male Wistar Albino rats were divided into six groups. Models of nerve injury, including blunt trauma, nerve incision, and autograft, were performed on all rats approximately 1 cm distal to the sciatic notch. B-complex vitamins were injected intraperitoneally at 0.2 mL/day to the treatment groups. The control groups were given 0.2 mL/day saline. After 1 month, the study was terminated, electromyography (EMG) was performed to measure the conduction velocity, and nerve tissue was taken from the repair line. The sciatic function indexes (SFIs) were calculated and analyzed. The histopathological samples were stained with hematoxylin and eosin and Toluidine blue and examined with a light microscope. Pathologically, myelination, fibrosis, edema, and mast cell densities in the nervous tissue were evaluated. Results: The vitamin B treatment groups demonstrated significant improvements in SFI compared to the control groups, indicating functional improvement in nerve damage (p < 0.05). In the nerve graft group, the vitamin B group showed a shorter latency, higher velocity, and larger peak-to-peak compared to the controls (p < 0.05). In the nerve transection group, the vitamin B group had better latency, velocity, and peak-to-peak values than the controls (p < 0.05). In the crush injury group, the vitamin B group exhibited an improved latency, velocity, and peak-to-peak compared to the controls (p < 0.05). Better myelination, less fibrosis, edema, and mast cells were also in the vitamin B group (p < 0.05). Conclusions: Vitamin B treatment significantly improves nerve healing and function in peripheral nerve injuries. It enhances nerve conduction, reduces fibrosis, and promotes myelination, indicating its therapeutic potential in nerve regeneration.
Assuntos
Modelos Animais de Doenças , Traumatismos dos Nervos Periféricos , Ratos Wistar , Complexo Vitamínico B , Animais , Ratos , Masculino , Traumatismos dos Nervos Periféricos/tratamento farmacológico , Traumatismos dos Nervos Periféricos/complicações , Complexo Vitamínico B/uso terapêutico , Complexo Vitamínico B/farmacologia , Eletromiografia , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/fisiologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Condução Nervosa/efeitos dos fármacosRESUMO
This study aimed to comprehensively explore the intricacies of corneal neurotization (CN) and the nuanced factors that set it apart from routine clinical practice, exerting a substantial influence on its success. A symbiotic relationship is evident between corneal innervation and ocular surface health. The loss of corneal innervation results in a potentially challenging corneal condition known as neurotrophic keratopathy (NK). The majority of treatments are primarily focused on preventing epithelial breakdown rather than addressing the underlying pathogenesis. Consequently, to address the impaired corneal sensation (underlying etiology), a novel surgical approach has emerged, namely CN, which involves transferring healthy sensory nerve axons to the affected cornea. This review offers valuable insights into the existing body of supporting evidence for CN, meticulously examining clinical studies, case reports, and experimental findings. The aim is to enhance our understanding of the effectiveness and potential outcomes associated with this innovative surgical technique. The exploration of innovative therapeutic avenues holds promise for revolutionizing the management of NK, offering a potentially permanent solution to a condition once deemed incurable and severely debilitating.
Assuntos
Córnea , Doenças da Córnea , Transferência de Nervo , Humanos , Córnea/inervação , Córnea/cirurgia , Doenças da Córnea/cirurgia , Doenças da Córnea/diagnóstico , Transferência de Nervo/métodos , Regeneração Nervosa/fisiologiaRESUMO
Adult central nervous system (CNS) neurons down-regulate growth programs after injury, leading to persistent regeneration failure. Coordinated lipids metabolism is required to synthesize membrane components during axon regeneration. However, lipids also function as cell signaling molecules. Whether lipid signaling contributes to axon regeneration remains unclear. In this study, we showed that lipin1 orchestrates mechanistic target of rapamycin (mTOR) and STAT3 signaling pathways to determine axon regeneration. We established an mTOR-lipin1-phosphatidic acid/lysophosphatidic acid-mTOR loop that acts as a positive feedback inhibitory signaling, contributing to the persistent suppression of CNS axon regeneration following injury. In addition, lipin1 knockdown (KD) enhances corticospinal tract (CST) sprouting after unilateral pyramidotomy and promotes CST regeneration following complete spinal cord injury (SCI). Furthermore, lipin1 KD enhances sensory axon regeneration after SCI. Overall, our research reveals that lipin1 functions as a central regulator to coordinate mTOR and STAT3 signaling pathways in the CNS neurons and highlights the potential of lipin1 as a promising therapeutic target for promoting the regeneration of motor and sensory axons after SCI.
Assuntos
Axônios , Neurônios Motores , Regeneração Nervosa , Fosfatidato Fosfatase , Fator de Transcrição STAT3 , Transdução de Sinais , Traumatismos da Medula Espinal , Serina-Treonina Quinases TOR , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/genética , Animais , Axônios/metabolismo , Axônios/fisiologia , Regeneração Nervosa/fisiologia , Fator de Transcrição STAT3/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fosfatidato Fosfatase/metabolismo , Fosfatidato Fosfatase/genética , Neurônios Motores/metabolismo , Neurônios Motores/fisiologia , Camundongos , Ácidos Fosfatídicos/metabolismo , Células Receptoras Sensoriais/metabolismo , Feminino , Tratos Piramidais/metabolismo , Tratos Piramidais/patologiaRESUMO
BACKGROUND: Limited treatment options exist for damaged nerves and despite impressive advances in tissue engineering, scientists and clinicians have yet to fully replicate nerve development and recruitment. Innervation is a critical feature for normal organ function. While most organs are innervated prior to birth, a rare example of postnatal nerve recruitment occurs in the natural development of secondary teeth during adolescence. Many animals undergo postnatal shedding of deciduous teeth with development and eruption of secondary teeth, a process requiring recruitment of nerve and vasculature to each tooth pulp for viability. Here, the investigators created a novel model for the study of postnatal innervation by exploiting the natural phenomenon of tooth-driven nerve recruitment. METHODS: The investigators theorized that developing teeth possess a special capacity to induce innervation which could be harnessed in a clinical setting for nerve regeneration, and hyptothesized that a transplant model could be created to capture this phenomenon. In this descriptive study, a rat model of autologous tooth transplantation and de novo nerve recruitment was developed by surgically transferring whole developing molars to the autologous tibia. RESULTS: Downstream histological analysis performed 6 to 14 weeks after surgery demonstrated integration of molar into tibia in 81% of postoperative rats, with progressive pulpal expression of nerve marker ß-tubulin III suggestive of neuronal recruitment. CONCLUSIONS: These findings provide a novel model for the study of organ transplantation and support the theory that developing dental tissues may retain nerve-inductive properties postnatally.
Assuntos
Transplante Autólogo , Animais , Ratos , Polpa Dentária/inervação , Polpa Dentária/citologia , Dente Molar , Modelos Animais , Regeneração Nervosa/fisiologia , Tíbia/cirurgia , Ratos Sprague-DawleyRESUMO
The in vivo three-dimensional genomic architecture of adult mature neurons at homeostasis and after medically relevant perturbations such as axonal injury remains elusive. Here, we address this knowledge gap by mapping the three-dimensional chromatin architecture and gene expression program at homeostasis and after sciatic nerve injury in wild-type and cohesin-deficient mouse sensory dorsal root ganglia neurons via combinatorial Hi-C, promoter-capture Hi-C, CUT&Tag for H3K27ac and RNA-seq. We find that genes involved in axonal regeneration form long-range, complex chromatin loops, and that cohesin is required for the full induction of the regenerative transcriptional program. Importantly, loss of cohesin results in disruption of chromatin architecture and severely impaired nerve regeneration. Complex enhancer-promoter loops are also enriched in the human fetal cortical plate, where the axonal growth potential is highest, and are lost in mature adult neurons. Together, these data provide an original three-dimensional chromatin map of adult sensory neurons in vivo and demonstrate a role for cohesin-dependent long-range promoter interactions in nerve regeneration.
Assuntos
Axônios , Cromatina , Coesinas , Regeneração Nervosa , Regiões Promotoras Genéticas , Células Receptoras Sensoriais , Animais , Células Receptoras Sensoriais/metabolismo , Células Receptoras Sensoriais/fisiologia , Camundongos , Regiões Promotoras Genéticas/genética , Cromatina/metabolismo , Regeneração Nervosa/genética , Regeneração Nervosa/fisiologia , Axônios/metabolismo , Axônios/fisiologia , Humanos , Proteínas Cromossômicas não Histona/metabolismo , Proteínas Cromossômicas não Histona/genética , Elementos Facilitadores Genéticos/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Gânglios Espinais/metabolismo , Gânglios Espinais/citologia , Nervo Isquiático/metabolismoRESUMO
Background/aim: In the literature, almost all of the nerve conduits proposed for obtaining better nerve recovery were applied as graft materials. In this study, we aimed to propose a new nerve conduit model with a flap pattern and evaluate the effect of a pedicled vascularized jejunal flap on nerve regeneration after wrapping it around a sciatic nerve. Materials and methods: A total of 90 Wistar albino rats were randomly divided into nine groups with 10 rats in each. The first three groups constituted the control groups, whereas Groups 4-6 were the jejunum conduit (JC)-applied groups. A mucosa-resected JC (MRJC) was applied in Groups 7 and 8. Epineurial neurorrhaphy was performed in Groups 1, 4, and 7; repair with a nerve graft was applied in Groups 2, 5, and 8; and a 1-cm-long nerve defect was created in Groups 3, 6, and 9. After 2 months of follow-up, nerve regeneration was assessed by statistical analyses of the Sciatic Functional Index (SFI) and histopathological evaluation. Results: The MRJC groups had significantly better results in terms of SFI (p = 0.005). Statistical differences in axonal degeneration, axonal density, myelination, and disorganization were found between all control groups and MRJC groups (p = 0.022, p = 0.001, p = 0.001, and p = 0.039, respectively). Conclusion: In this study, the feasibility of wrapping around the nerve repair zones of pedicled autologous flaps designed in a tubular fashion was observed in a small rat model. The findings must be further validated with larger animals before clinical testing.
Assuntos
Jejuno , Regeneração Nervosa , Ratos Wistar , Nervo Isquiático , Retalhos Cirúrgicos , Animais , Regeneração Nervosa/fisiologia , Ratos , Nervo Isquiático/cirurgia , Jejuno/cirurgia , MasculinoRESUMO
Recent studies highlighted the role of platelet-rich plasma (PRP) in progenitor cell homing, migration, and nerve cell regeneration while also inhibiting fibrosis and apoptosis in cavernous nerve injury (CNI). The aim of this study was to investigate the effect of PRP administration on axon and collagen regeneration in CNI. A true experimental study using a post-test-only control group design was conducted. Twenty-five male Wistar rats (Rattus norvegicus), weighing 200-300 grams, were divided into five groups: two control groups (sham procedure and negative control), and three experimental groups receiving local PRP, intraperitoneal PRP, and a combination of local and intraperitoneal PRP. The cavernous nerve was injured with a hemostasis clamp for one minute before 200 µL of 200 PRP was injected locally, intraperitoneally, or both, depending on the group. After four weeks, the rats were euthanized, tissue segments (2 mm) from each cavernous nerve and mid-penis were collected and analyzed for collagen density, axon diameter, and number of myelinated axons. Our study found that collagen growth was slower in CNI group without PRP (sham procedure) compared to all PRP groups (local, intraperitoneal, and combination). The intraperitoneal PRP group had the highest collagen density at 5.62 µm; however, no significant difference was observed in collagen density among all groups (p=0.056). Similar axon diameter was found across the groups, with no statistically significant difference observed (p=0.856). In the number of myelinated axons, a significant difference was found among all groups with significantly more axons in local PRP and combined local and intraperitoneal PRP groups compared to others (p=0.026). In conclusion, PRP administration improved the number of myelinated axons in CNI, suggesting PRP role in CNI regeneration and the potential for an innovative approach to treating erectile dysfunction associated with CNI.
Assuntos
Axônios , Colágeno , Disfunção Erétil , Regeneração Nervosa , Pênis , Plasma Rico em Plaquetas , Ratos Wistar , Animais , Masculino , Colágeno/metabolismo , Ratos , Regeneração Nervosa/efeitos dos fármacos , Regeneração Nervosa/fisiologia , Axônios/fisiologia , Axônios/patologia , Axônios/efeitos dos fármacos , Pênis/inervação , Pênis/efeitos dos fármacos , Disfunção Erétil/terapia , Disfunção Erétil/tratamento farmacológico , Modelos Animais de Doenças , Traumatismos dos Nervos Periféricos/terapiaRESUMO
Most neurons are not replaced after injury and thus possess robust intrinsic mechanisms for repair after damage. Axon injury triggers a calcium wave, and calcium and cAMP can augment axon regeneration. In comparison to axon regeneration, dendrite regeneration is poorly understood. To test whether calcium and cAMP might also be involved in dendrite injury signaling, we tracked the responses of Drosophila dendritic arborization neurons to laser severing of axons and dendrites. We found that calcium and subsequently cAMP accumulate in the cell body after both dendrite and axon injury. Two voltage-gated calcium channels (VGCCs), L-Type and T-Type, are required for the calcium influx in response to dendrite injury and play a role in rapid initiation of dendrite regeneration. The AC8 family adenylyl cyclase, Ac78C, is required for cAMP production after dendrite injury and timely initiation of regeneration. Injury-induced cAMP production is sensitive to VGCC reduction, placing calcium upstream of cAMP generation. We propose that two VGCCs initiate global calcium influx in response to dendrite injury followed by production of cAMP by Ac78C. This signaling pathway promotes timely initiation of dendrite regrowth several hours after dendrite damage.
Assuntos
Adenilil Ciclases , Canais de Cálcio Tipo L , Cálcio , AMP Cíclico , Dendritos , Animais , Adenilil Ciclases/metabolismo , Adenilil Ciclases/genética , Axônios/metabolismo , Axônios/fisiologia , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Canais de Cálcio/genética , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo L/genética , Canais de Cálcio Tipo T/metabolismo , Canais de Cálcio Tipo T/genética , Sinalização do Cálcio/genética , AMP Cíclico/metabolismo , Dendritos/metabolismo , Drosophila/genética , Drosophila melanogaster/genética , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Regeneração Nervosa/fisiologia , Regeneração Nervosa/genética , Neurônios/metabolismo , Regeneração/genética , Regeneração/fisiologia , Transdução de SinaisRESUMO
Myelin is an insulator that forms around axons that enhance the conduction velocity of nerve fibers. Oligodendrocytes dramatically change cell morphology to produce myelin throughout the central nervous system (CNS). Cytoskeletal alterations are critical for the morphogenesis of oligodendrocytes, and actin is involved in cell differentiation and myelin wrapping via polymerization and depolymerization, respectively. Various protein members of the myosin superfamily are known to be major binding partners of actin filaments and have been intensively researched because of their involvement in various cellular functions, including differentiation, cell movement, membrane trafficking, organelle transport, signal transduction, and morphogenesis. Some members of the myosin superfamily have been found to play important roles in the differentiation of oligodendrocytes and in CNS myelination. Interestingly, each member of the myosin superfamily expressed in oligodendrocyte lineage cells also shows specific spatial and temporal expression patterns and different distributions. In this review, we summarize previous findings related to the myosin superfamily and discuss how these molecules contribute to myelin formation and regeneration by oligodendrocytes.
Assuntos
Bainha de Mielina , Miosinas , Oligodendroglia , Animais , Humanos , Bainha de Mielina/metabolismo , Bainha de Mielina/fisiologia , Miosinas/metabolismo , Oligodendroglia/metabolismo , Oligodendroglia/fisiologia , Regeneração Nervosa/fisiologia , Diferenciação Celular/fisiologiaRESUMO
Adult zebrafish have an innate ability to recover from severe spinal cord injury. Here, we report a comprehensive single nuclear RNA sequencing atlas that spans 6 weeks of regeneration. We identify cooperative roles for adult neurogenesis and neuronal plasticity during spinal cord repair. Neurogenesis of glutamatergic and GABAergic neurons restores the excitatory/inhibitory balance after injury. In addition, a transient population of injury-responsive neurons (iNeurons) show elevated plasticity 1 week post-injury. We found iNeurons are injury-surviving neurons that acquire a neuroblast-like gene expression signature after injury. CRISPR/Cas9 mutagenesis showed iNeurons are required for functional recovery and employ vesicular trafficking as an essential mechanism that underlies neuronal plasticity. This study provides a comprehensive resource of the cells and mechanisms that direct spinal cord regeneration and establishes zebrafish as a model of plasticity-driven neural repair.
Assuntos
Neurogênese , Plasticidade Neuronal , Análise de Célula Única , Traumatismos da Medula Espinal , Regeneração da Medula Espinal , Medula Espinal , Peixe-Zebra , Animais , Traumatismos da Medula Espinal/metabolismo , Plasticidade Neuronal/fisiologia , Neurogênese/genética , Medula Espinal/metabolismo , Neurônios/metabolismo , Neurônios/fisiologia , Sistemas CRISPR-Cas , Neurônios GABAérgicos/metabolismo , Recuperação de Função Fisiológica , Modelos Animais de Doenças , Regeneração Nervosa/fisiologia , Animais Geneticamente ModificadosRESUMO
Upper extremity amputation can lead to significant functional morbidity. The main goals after amputation are to minimize pain and maintain or improve functional status while optimizing the quality of life. Postamputation pain is common and can be addressed with regenerative peripheral nerve interface surgery or targeted muscle reinnervation surgery. Both modalities are effective in treating residual limb pain and phantom limb pain, as well as improving prosthetic use. Differences in surgical technique between the 2 approaches need to be weighed when deciding what strategy may be most appropriate for the patient.