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Retrograde viral transduction of cortical pyramidal neurons from the spinal cord

Groutsi, F; Mason, MRJ; Anderson, PN; Martins, S; Anesti, M; Coffin, RS; Campbell, G; (2008) Retrograde viral transduction of cortical pyramidal neurons from the spinal cord. RESTOR NEUROL NEUROS , 26 (6) 509 - 520.

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Abstract

Purpose: The primary motor pathway, the corticospinal tract, is a major target for spinal cord regeneration studies. One way of improving the regeneration of corticospinal axons is to introduce regeneration-associated genes into cortical motor neurons using viral vector delivery.Methods: We used an engineered Herpes Simplex virus (HSV1) with the EF1 alpha promoter encoding either LacZ or GFP to transduce cortical neurons through retrograde transport following the injection of vector into adult rat striatum or spinal cord. After three-days to one-month post-injection, sections of brain and spinal cord were viewed with fluorescence microscopy or processed for LacZ histochemistry.Results: Many layer V motor cortical neurons were transduced following striatal injections. These were not corticospinal neurons as they were not fluorogold-labelled following tracer injection into spinal cord. Corticospinal neurons in both hemispheres were, however, transduced following direct vector injections into the dorsal column of spinal cord, yielding 250-400 transduced corticospinal neurons per animal. No non-pyramidal neurons or thalamic neurons were transduced by spinal injections.Conclusions: Therefore, this HSV1. EF1 alpha vector is highly effective for the transduction of corticospinal neurons without direct injection into the brain and could be used to introduce regeneration-relevant genes into these neurons with the aim of regenerating the corticospinal tract.

Type: Article
Title: Retrograde viral transduction of cortical pyramidal neurons from the spinal cord
Keywords: In vivo transduction, corticospinal neurons, HSV1 vector, elongation factor 1 alpha, rat, POSTTRANSCRIPTIONAL REGULATORY ELEMENT, SIMPLEX VIRUS TYPE-1, CENTRAL-NERVOUS-SYSTEM, TEMPERATURE-SENSITIVE MUTANTS, EARLY GENE-EXPRESSION, TRANSGENE EXPRESSION, IN-VIVO, AXONAL REGENERATION, CELL TROPISM, RAT-BRAIN
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > UCL Medical School
URI: http://discovery.ucl.ac.uk/id/eprint/165300
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