Lentiviral Vector Delivery of Short Hairpin RNA to NgR1 Promotes Nerve Regeneration and Locomotor Recovery in Injured Rat Spinal Cord

Overview

Journal Sci Rep

Specialty Science

Date 2018 Apr 5

PMID 29615686

Citations 5

Authors

Xiaoyang Zhao

Zhiming Peng

Lingli Long

Ningning Chen

Haichong Zheng

David Y B Deng

Yong Wan

Affiliations

Soon will be listed here.

Abstract

Nogo receptor 1 (NgR1) is a high-affinity receptor of myelin-associated inhibitors (MAIs), and suppresses neurogenesis. Lentiviral vector are commonly used to alter the expression of targeted genes. However, little is known about the potential function of lentiviral vector harboring NgR1 shRNA (LV-NgR1 shRNA) on neurogenesis in spinal cord injury (SCI). In this study, the rats were randomly divided into three groups: including the LN (LV-NgR1 shRNA injection), LC (LV-control shRNA injection) and Sham (laminectomy only). Eight weeks post-injection of LV, spinal cords were examined by histology for changes in cavity size and by immunohistochemistry for changes in expression of NgR1, cell apoptosis, astrocytes, neurons and myelination. Motor function was assessed using the Basso, Beattie and Bresnahan (BBB) locomotor scale. Animals that received LV-NgR1 shRNA remarkably improved the motor function. These animals also showed an increase in levels of nerve fibers, synapses and myelination, a decrease in levels of lesion cavity and cell apoptosis at 8 weeks post-treatment. These findings give evidence that NgR1 may be a promising target for SCI treatment.

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References

Ji B, Li M, Wu W, Yick L, Lee X, Shao Z . LINGO-1 antagonist promotes functional recovery and axonal sprouting after spinal cord injury. Mol Cell Neurosci. 2006; 33(3):311-20. DOI: 10.1016/j.mcn.2006.08.003. View

Yuan Y, He C . The glial scar in spinal cord injury and repair. Neurosci Bull. 2013; 29(4):421-35. PMC: 5561940. DOI: 10.1007/s12264-013-1358-3. View

Li M, Ona V, Chen M, Kaul M, Tenneti L, Zhang X . Functional role and therapeutic implications of neuronal caspase-1 and -3 in a mouse model of traumatic spinal cord injury. Neuroscience. 2000; 99(2):333-42. DOI: 10.1016/s0306-4522(00)00173-1. View

Fu Q, Liao X, Li X, Chen D, Shi J, Wen W . Soluble Nogo-66 receptor prevents synaptic dysfunction and rescues retinal ganglion cell loss in chronic glaucoma. Invest Ophthalmol Vis Sci. 2011; 52(11):8374-80. DOI: 10.1167/iovs.11-7667. View

Kopp M, Liebscher T, Niedeggen A, Laufer S, Brommer B, Jungehulsing G . Small-molecule-induced Rho-inhibition: NSAIDs after spinal cord injury. Cell Tissue Res. 2012; 349(1):119-32. PMC: 3744771. DOI: 10.1007/s00441-012-1334-7. View

Walker C, Xu X . PTEN inhibitor bisperoxovanadium protects oligodendrocytes and myelin and prevents neuronal atrophy in adult rats following cervical hemicontusive spinal cord injury. Neurosci Lett. 2014; 573:64-8. PMC: 4055541. DOI: 10.1016/j.neulet.2014.02.039. View

Li Z, Tang R, Zhang J, Tang Z, Qu W, Zhu W . Inhibiting epidermal growth factor receptor attenuates reactive astrogliosis and improves functional outcome after spinal cord injury in rats. Neurochem Int. 2011; 58(7):812-9. DOI: 10.1016/j.neuint.2011.03.007. View

McKerracher L, David S, Jackson D, Kottis V, Dunn R, Braun P . Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth. Neuron. 1994; 13(4):805-11. DOI: 10.1016/0896-6273(94)90247-x. View

Bo X, Wu D, Yeh J, Zhang Y . Gene therapy approaches for neuroprotection and axonal regeneration after spinal cord and spinal root injury. Curr Gene Ther. 2011; 11(2):101-15. DOI: 10.2174/156652311794940773. View

10.

McDonald J, Liu X, Qu Y, Liu S, Mickey S, Turetsky D . Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat Med. 1999; 5(12):1410-2. DOI: 10.1038/70986. View

11.

Ukai J, Imagama S, Ohgomori T, Ito Z, Ando K, Ishiguro N . Nogo receptor 1 is expressed in both primary cultured glial cells and neurons. Nagoya J Med Sci. 2016; 78(3):303-11. PMC: 4995276. View

12.

Scherr M, Battmer K, Ganser A, Eder M . Modulation of gene expression by lentiviral-mediated delivery of small interfering RNA. Cell Cycle. 2003; 2(3):251-7. View

13.

Saha N, Kolev M, Nikolov D . Structural features of the Nogo receptor signaling complexes at the neuron/myelin interface. Neurosci Res. 2014; 87:1-7. DOI: 10.1016/j.neures.2014.06.003. View

14.

Wang K, Koprivica V, Kim J, Sivasankaran R, Guo Y, Neve R . Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. Nature. 2002; 417(6892):941-4. DOI: 10.1038/nature00867. View

15.

Sakuma T, Barry M, Ikeda Y . Lentiviral vectors: basic to translational. Biochem J. 2012; 443(3):603-18. DOI: 10.1042/BJ20120146. View

16.

Wang X, Yigitkanli K, Kim C, Sekine-Komo T, Wirak D, Frieden E . Human NgR-Fc decoy protein via lumbar intrathecal bolus administration enhances recovery from rat spinal cord contusion. J Neurotrauma. 2014; 31(24):1955-66. PMC: 4245872. DOI: 10.1089/neu.2014.3355. View

17.

Liu X, Zuo Z, Liu W, Wang Z, Hou Y, Fu Y . Upregulation of Nogo receptor expression induces apoptosis of retinal ganglion cells in diabetic rats. Neural Regen Res. 2014; 9(8):815-20. PMC: 4146255. DOI: 10.4103/1673-5374.131597. View

18.

Peng Y, Zhang Q, Xu D, Wang Y, Qin X . Small hairpin RNA interference of the Nogo receptor inhibits oxygen-glucose deprivation-induced damage in rat hippocampal slice cultures. Neuropathology. 2010; 30(6):565-73. DOI: 10.1111/j.1440-1789.2010.01102.x. View

19.

Cua R, Lau L, Keough M, Midha R, Apte S, Yong V . Overcoming neurite-inhibitory chondroitin sulfate proteoglycans in the astrocyte matrix. Glia. 2013; 61(6):972-84. DOI: 10.1002/glia.22489. View

20.

Deng Q, Cai W, Li S, Su B . Identification of a NEP1-35 recognizing peptide that neutralizes CNS myelin inhibition using phage display library. Neurosci Lett. 2013; 536:80-4. DOI: 10.1016/j.neulet.2013.01.009. View