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Enhanced adenoviral gene delivery to motor and dorsal root ganglion neurons following injection into demyelinated peripheral nerves

Injection of viral vectors into peripheral nerves may transfer specific genes into their dorsal root ganglion (DRG) neurons and motoneurons. However, myelin sheaths of peripheral axons block the entry of viral particles into nerves. We studied whether mild, transient peripheral nerve demyelination prior to intraneural viral vector injection would enhance gene transfer to target DRG neurons and motoneurons. The right sciatic nerve of C57BL/6 mice was focally demyelinated with 1% lysolecithin, and the left sciatic nerve was similarly injected with saline (control). Five days after demyelination, 0.5 microl of Ad5-GFP was injected into both sciatic nerves at the site of previous injection. The effectiveness of gene transfer was evaluated by counting GFP(+) neurons in the DRGs and ventral horns. After peripheral nerve demyelination, there was a fivefold increase in the number of infected DRG neurons and almost a 15-fold increase in the number of infected motoneurons compared with the control, nondemyelinated side. Focal demyelination reduced the myelin sheath barrier, allowing greater virus-axon contact. Increased CXADR expression on the demyelinated axons facilitated axoplasmic viral entry. No animals sustained any prolonged neurological deficits. Increased gene delivery into DRG neurons and motoneurons may provide effective treatment for amyotrophic lateral sclerosis, pain, and spinal cord injury

Keywords : Adenoviridae,Animals,Axons,Blotting,Western,chemically induced,Demyelinating Diseases,Enterovirus,Female,Ganglia,Spinal,Gene Transfer Techniques,genetics,Green Fluorescent Proteins,Immunohistochemistry,injuries,Locomotion,Lysophosphatidylcholines,metabolism,Mice,Mice,Inbred C57BL,Motor Neurons,Neuritis,Neurons,Pain,pathology,Peripheral Nerves,physiology,Receptors,Virus,Sciatic Nerve,Sensation,Spinal Cord,Spinal Cord Injuries,, Adenoviral,Gene,Delivery,Motor, disc replacement surgery

Date of Publication : 2010 Aug 15

Authors : Zhang Y;Zheng Y;Zhang YP;Shields LB;Hu X;Yu P;Burke DA;Wang H;Jun C;Byers J;Whittemore SR;Shields CB;

Organisation : Kentucky Spinal Cord Injury Research Center, Louisville, Kentucky, USA

Journal of Publication : J Neurosci Res

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/20623527

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