axonal growth
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BMC Biology ◽  
2022 ◽  
Vol 20 (1) ◽  
Soyeon Lee ◽  
Dongkeun Park ◽  
Chunghun Lim ◽  
Jae-Ick Kim ◽  
Kyung-Tai Min

Abstract Background The establishment and maintenance of functional neural connections relies on appropriate distribution and localization of mitochondria in neurites, as these organelles provide essential energy and metabolites. In particular, mitochondria are transported to axons and support local energy production to maintain energy-demanding neuronal processes including axon branching, growth, and regeneration. Additionally, local protein synthesis is required for structural and functional changes in axons, with nuclear-encoded mitochondrial mRNAs having been found localized in axons. However, it remains unclear whether these mRNAs are locally translated and whether the potential translated mitochondrial proteins are involved in the regulation of mitochondrial functions in axons. Here, we aim to further understand the purpose of such compartmentalization by focusing on the role of mitochondrial initiation factor 3 (mtIF3), whose nuclear-encoded transcripts have been shown to be present in axonal growth cones. Results We demonstrate that brain-derived neurotrophic factor (BDNF) induces local translation of mtIF3 mRNA in axonal growth cones. Subsequently, mtIF3 protein is translocated into axonal mitochondria and promotes mitochondrial translation as assessed by our newly developed bimolecular fluorescence complementation sensor for the assembly of mitochondrial ribosomes. We further show that BDNF-induced axonal growth requires mtIF3-dependent mitochondrial translation in distal axons. Conclusion We describe a previously unknown function of mitochondrial initiation factor 3 (mtIF3) in axonal protein synthesis and development. These findings provide insight into the way neurons adaptively control mitochondrial physiology and axonal development via local mtIF3 translation.

Junhao Lin ◽  
Jie Shi ◽  
Xiang Min ◽  
Si Chen ◽  
Yunpeng Zhao ◽  

Introduction: Sciatic nerve injury is a common injury of the nervous system. Stem cell-based therapies, drug-based therapies and rehabilitation physiotherapy therapies are currently available, but their limited therapeutic efficacy limits their use. Here, we aimed to explore a novel lentiviral-based gene therapeutic strategy and to elaborate its mechanism.Materials and Methods: Recombinant GDF11 protein was used for the in vitro treatment of dorsal root ganglion (DRG) cells. Lentivirus was used to construct a vector system for the in vivo expression of GDF11. The nerve conduction function was detected using action-evoked potentials at different time periods, and the regulatory effect of nerves on target organs was detected by weighing the gastrocnemius muscle. Immunofluorescence of NF200 and S100 was used to show the regeneration of the sciatic nerve, and myelin and Nissl staining were performed to observe the pathological features of the tissue. Western was used to validate signaling pathways. The expression of related genes was observed by qPCR and Western blotting, and cell apoptosis was detected by flow cytometry.Result: GDF11 promotes the axonal growth of DRG cells and inhibits DGR cell apoptosis in vitro. GDF11 acts by activating the Smad pathway. GDF11 promotes the recovery of damaged sciatic nerve function in rats, the regeneration of damaged sciatic nerves in rats, and myelin regeneration of damaged sciatic nerves in rats. GDF11 also exerts a protective effect on neuronal cells in rats.Conclusion: Based on the present study, we conclude that GDF11 promotes axonal growth and inhibits DRG cell apoptosis in vitro through the Smad pathway, and lentivirus-mediated GDF11 overexpression in vivo can promote the recovery of sciatic nerves after transection by promoting axonal growth and inhibiting neuronal apoptosis in the spinal cord.

Gels ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. 25
Devindraan Sirkkunan ◽  
Belinda Pingguan-Murphy ◽  
Farina Muhamad

Tissues are commonly defined as groups of cells that have similar structure and uniformly perform a specialized function. A lesser-known fact is that the placement of these cells within these tissues plays an important role in executing its functions, especially for neuronal cells. Hence, the design of a functional neural scaffold has to mirror these cell organizations, which are brought about by the configuration of natural extracellular matrix (ECM) structural proteins. In this review, we will briefly discuss the various characteristics considered when making neural scaffolds. We will then focus on the cellular orientation and axonal alignment of neural cells within their ECM and elaborate on the mechanisms involved in this process. A better understanding of these mechanisms could shed more light onto the rationale of fabricating the scaffolds for this specific functionality. Finally, we will discuss the scaffolds used in neural tissue engineering (NTE) and the methods used to fabricate these well-defined constructs.

2021 ◽  
Pamela Meneses Iack ◽  
Danielle Rayêe ◽  
Roberto Lent ◽  
Victor Túlio Ribeiro‐Resende ◽  
Patrícia P. Garcez

2021 ◽  
Vol 10 (10) ◽  
pp. 16
Anat Nitzan ◽  
Miriam Corredor-Sanchez ◽  
Ronit Galron ◽  
Limor Nahary ◽  
Mary Safrin ◽  

2021 ◽  
Feng Wang ◽  
Xinya Fu ◽  
Meiemei Li ◽  
Xingran Wang ◽  
Jile Xie ◽  

The loss of motor function in patients with spinal cord injury (SCI) is primarily due to the severing of the corticospinal tract (CST). Spinal motor neurons are located in the anterior horn of the spinal cord, and as the lower neurons of the CST, they control voluntary movement. Furthermore, its intrinsic axonal growth ability is significantly stronger than that of cerebral cortex pyramid neurons, which are the upper CST neurons. Therefore, we established an axonal regeneration model of spinal motor neurons to investigate the feasibility of repairing SCI by promoting axonal regeneration of spinal motor neurons. We demonstrated that conditionally knocking out pten in mature spinal motor neurons drastically enhanced axonal regeneration in vivo, and the regenerating axons of the spinal motor neurons re-established synapses with other cells in the damaged spinal cord. Thus, this strategy may serve as a novel and effective treatment method for SCI.

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