Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury

Marc J Ruitenberg; Bas Blits; Paul A Dijkhuizen; Erik T te Beek; Arne Bakker; Joop J van Heerikhuize; Chris W Pool; Wim T J M C Hermens; Gerard J Boer; J. Verhaagen

doi:10.1016/j.nbd.2003.11.018

Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury

Marc J Ruitenberg, Bas Blits, Paul A Dijkhuizen, Erik T te Beek, Arne Bakker, Joop J van Heerikhuize, Chris W Pool, Wim T J M C Hermens, Gerard J Boer, J. Verhaagen

Netherlands Institute for Neuroscience (NIN)

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

Abstract

Rubrospinal neurons (RSNs) undergo marked atrophy after cervical axotomy. This progressive atrophy may impair the regenerative capacity of RSNs in response to repair strategies that are targeted to promote rubrospinal tract regeneration. Here, we investigated whether we could achieve long-term rescue of RSNs from lesion-induced atrophy by adeno-associated viral (AAV) vector-mediated gene transfer of brain-derived neurotrophic factor (BDNF). We show for the first time that AAV vectors can be used for the persistent transduction of highly atrophic neurons in the red nucleus (RN) for up to 18 months after injury. Furthermore, BDNF gene transfer into the RN following spinal axotomy resulted in counteraction of atrophy in both the acute and chronic stage after injury. These novel findings demonstrate that a gene therapeutic approach can be used to reverse atrophy of lesioned CNS neurons for an extended period of time.

Original language	English
Pages (from-to)	394-406
Number of pages	13
Journal	Neurobiology of Disease
Volume	15
Issue number	2
DOIs	https://doi.org/10.1016/j.nbd.2003.11.018
Publication status	Published - Mar 2004

Keywords

Acute Disease
Animals
Atrophy
Axotomy
Brain-Derived Neurotrophic Factor
Chronic Disease
Dependovirus
Disease Models, Animal
Efferent Pathways
Gene Transfer Techniques
Genetic Vectors
Male
Nerve Regeneration
Neurons
Rats
Reaction Time
Receptor, trkB
Red Nucleus
Retrograde Degeneration
Spinal Cord
Spinal Cord Injuries
Journal Article
Research Support, Non-U.S. Gov't

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Ruitenberg, M. J., Blits, B., Dijkhuizen, P. A., te Beek, E. T., Bakker, A., van Heerikhuize, J. J., Pool, C. W., Hermens, W. T. J. M. C., Boer, G. J., & Verhaagen, J. (2004). Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury. Neurobiology of Disease, 15(2), 394-406. https://doi.org/10.1016/j.nbd.2003.11.018

Ruitenberg, Marc J ; Blits, Bas ; Dijkhuizen, Paul A ; te Beek, Erik T ; Bakker, Arne ; van Heerikhuize, Joop J ; Pool, Chris W ; Hermens, Wim T J M C ; Boer, Gerard J ; Verhaagen, J. / Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury. In: Neurobiology of Disease. 2004 ; Vol. 15, No. 2. pp. 394-406.

@article{236546698e2043f9a2b455dc86a8d849,

title = "Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury",

abstract = "Rubrospinal neurons (RSNs) undergo marked atrophy after cervical axotomy. This progressive atrophy may impair the regenerative capacity of RSNs in response to repair strategies that are targeted to promote rubrospinal tract regeneration. Here, we investigated whether we could achieve long-term rescue of RSNs from lesion-induced atrophy by adeno-associated viral (AAV) vector-mediated gene transfer of brain-derived neurotrophic factor (BDNF). We show for the first time that AAV vectors can be used for the persistent transduction of highly atrophic neurons in the red nucleus (RN) for up to 18 months after injury. Furthermore, BDNF gene transfer into the RN following spinal axotomy resulted in counteraction of atrophy in both the acute and chronic stage after injury. These novel findings demonstrate that a gene therapeutic approach can be used to reverse atrophy of lesioned CNS neurons for an extended period of time.",

keywords = "Acute Disease, Animals, Atrophy, Axotomy, Brain-Derived Neurotrophic Factor, Chronic Disease, Dependovirus, Disease Models, Animal, Efferent Pathways, Gene Transfer Techniques, Genetic Vectors, Male, Nerve Regeneration, Neurons, Rats, Reaction Time, Receptor, trkB, Red Nucleus, Retrograde Degeneration, Spinal Cord, Spinal Cord Injuries, Journal Article, Research Support, Non-U.S. Gov't",

author = "Ruitenberg, {Marc J} and Bas Blits and Dijkhuizen, {Paul A} and {te Beek}, {Erik T} and Arne Bakker and {van Heerikhuize}, {Joop J} and Pool, {Chris W} and Hermens, {Wim T J M C} and Boer, {Gerard J} and J. Verhaagen",

year = "2004",

month = mar,

doi = "10.1016/j.nbd.2003.11.018",

language = "English",

volume = "15",

pages = "394--406",

journal = "Neurobiology of Disease",

issn = "0969-9961",

publisher = "Academic Press",

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Ruitenberg, MJ, Blits, B, Dijkhuizen, PA, te Beek, ET, Bakker, A, van Heerikhuize, JJ, Pool, CW, Hermens, WTJMC, Boer, GJ & Verhaagen, J 2004, 'Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury', Neurobiology of Disease, vol. 15, no. 2, pp. 394-406. https://doi.org/10.1016/j.nbd.2003.11.018

Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury. / Ruitenberg, Marc J; Blits, Bas; Dijkhuizen, Paul A; te Beek, Erik T; Bakker, Arne; van Heerikhuize, Joop J; Pool, Chris W; Hermens, Wim T J M C; Boer, Gerard J; Verhaagen, J.

In: Neurobiology of Disease, Vol. 15, No. 2, 03.2004, p. 394-406.

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

TY - JOUR

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AU - Ruitenberg, Marc J

AU - Blits, Bas

AU - Dijkhuizen, Paul A

AU - te Beek, Erik T

AU - Bakker, Arne

AU - van Heerikhuize, Joop J

AU - Pool, Chris W

AU - Hermens, Wim T J M C

AU - Boer, Gerard J

AU - Verhaagen, J.

PY - 2004/3

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N2 - Rubrospinal neurons (RSNs) undergo marked atrophy after cervical axotomy. This progressive atrophy may impair the regenerative capacity of RSNs in response to repair strategies that are targeted to promote rubrospinal tract regeneration. Here, we investigated whether we could achieve long-term rescue of RSNs from lesion-induced atrophy by adeno-associated viral (AAV) vector-mediated gene transfer of brain-derived neurotrophic factor (BDNF). We show for the first time that AAV vectors can be used for the persistent transduction of highly atrophic neurons in the red nucleus (RN) for up to 18 months after injury. Furthermore, BDNF gene transfer into the RN following spinal axotomy resulted in counteraction of atrophy in both the acute and chronic stage after injury. These novel findings demonstrate that a gene therapeutic approach can be used to reverse atrophy of lesioned CNS neurons for an extended period of time.

AB - Rubrospinal neurons (RSNs) undergo marked atrophy after cervical axotomy. This progressive atrophy may impair the regenerative capacity of RSNs in response to repair strategies that are targeted to promote rubrospinal tract regeneration. Here, we investigated whether we could achieve long-term rescue of RSNs from lesion-induced atrophy by adeno-associated viral (AAV) vector-mediated gene transfer of brain-derived neurotrophic factor (BDNF). We show for the first time that AAV vectors can be used for the persistent transduction of highly atrophic neurons in the red nucleus (RN) for up to 18 months after injury. Furthermore, BDNF gene transfer into the RN following spinal axotomy resulted in counteraction of atrophy in both the acute and chronic stage after injury. These novel findings demonstrate that a gene therapeutic approach can be used to reverse atrophy of lesioned CNS neurons for an extended period of time.

KW - Acute Disease

KW - Animals

KW - Atrophy

KW - Axotomy

KW - Brain-Derived Neurotrophic Factor

KW - Chronic Disease

KW - Dependovirus

KW - Disease Models, Animal

KW - Efferent Pathways

KW - Gene Transfer Techniques

KW - Genetic Vectors

KW - Male

KW - Nerve Regeneration

KW - Neurons

KW - Rats

KW - Reaction Time

KW - Receptor, trkB

KW - Red Nucleus

KW - Retrograde Degeneration

KW - Spinal Cord

KW - Spinal Cord Injuries

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.nbd.2003.11.018

DO - 10.1016/j.nbd.2003.11.018

M3 - Article

C2 - 15006710

VL - 15

SP - 394

EP - 406

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

IS - 2

ER -