Tags

Type your tag names separated by a space and hit enter

Differential effects of lentiviral vector-mediated overexpression of nerve growth factor and glial cell line-derived neurotrophic factor on regenerating sensory and motor axons in the transected peripheral nerve.
Eur J Neurosci. 2008 Oct; 28(8):1467-79.EJ

Abstract

Even after reconstructive surgery, major functional impairments remain in the majority of patients with peripheral nerve injuries. The application of novel emerging therapeutic strategies, such as lentiviral (LV) vectors, may help to stimulate peripheral nerve regeneration at a molecular level. In the experiments described here, we examined the effect of LV vector-mediated overexpression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) on regeneration of the rat peripheral nerve in a transection/repair model in vivo. We showed that LV vectors can be used to locally elevate levels of NGF and GDNF in the injured rat peripheral nerve and this has profound and differential effects on regenerating sensory and motor neurons. For sensory neurons, increased levels of NGF and GDNF do not affect the number of regenerated neurons 1 cm distal to a lesion at 4 weeks post-lesion but do cause changes in the expression of markers for different populations of nociceptive neurons. These changes are accompanied by significant alterations in the recovery of nociceptive function. For motoneurons, overexpression of GDNF causes trapping of regenerating axons, impairing both long-distance axonal outgrowth and reinnervation of target muscles, whereas NGF has no effect on these parameters. These observations show the feasibility of combining surgical repair of the transected nerve with the application of viral vectors. Furthermore, they show a difference between the regenerative responses of motor and sensory neurons to locally increased levels of NGF and GDNF.

Authors+Show Affiliations

Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18973572

Citation

Tannemaat, Martijn R., et al. "Differential Effects of Lentiviral Vector-mediated Overexpression of Nerve Growth Factor and Glial Cell Line-derived Neurotrophic Factor On Regenerating Sensory and Motor Axons in the Transected Peripheral Nerve." The European Journal of Neuroscience, vol. 28, no. 8, 2008, pp. 1467-79.
Tannemaat MR, Eggers R, Hendriks WT, et al. Differential effects of lentiviral vector-mediated overexpression of nerve growth factor and glial cell line-derived neurotrophic factor on regenerating sensory and motor axons in the transected peripheral nerve. Eur J Neurosci. 2008;28(8):1467-79.
Tannemaat, M. R., Eggers, R., Hendriks, W. T., de Ruiter, G. C., van Heerikhuize, J. J., Pool, C. W., Malessy, M. J., Boer, G. J., & Verhaagen, J. (2008). Differential effects of lentiviral vector-mediated overexpression of nerve growth factor and glial cell line-derived neurotrophic factor on regenerating sensory and motor axons in the transected peripheral nerve. The European Journal of Neuroscience, 28(8), 1467-79. https://doi.org/10.1111/j.1460-9568.2008.06452.x
Tannemaat MR, et al. Differential Effects of Lentiviral Vector-mediated Overexpression of Nerve Growth Factor and Glial Cell Line-derived Neurotrophic Factor On Regenerating Sensory and Motor Axons in the Transected Peripheral Nerve. Eur J Neurosci. 2008;28(8):1467-79. PubMed PMID: 18973572.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential effects of lentiviral vector-mediated overexpression of nerve growth factor and glial cell line-derived neurotrophic factor on regenerating sensory and motor axons in the transected peripheral nerve. AU - Tannemaat,Martijn R, AU - Eggers,Ruben, AU - Hendriks,William T, AU - de Ruiter,Godard C W, AU - van Heerikhuize,Joop J, AU - Pool,Chris W, AU - Malessy,Martijn J A, AU - Boer,Gerard J, AU - Verhaagen,Joost, PY - 2008/11/1/pubmed PY - 2009/1/27/medline PY - 2008/11/1/entrez SP - 1467 EP - 79 JF - The European journal of neuroscience JO - Eur. J. Neurosci. VL - 28 IS - 8 N2 - Even after reconstructive surgery, major functional impairments remain in the majority of patients with peripheral nerve injuries. The application of novel emerging therapeutic strategies, such as lentiviral (LV) vectors, may help to stimulate peripheral nerve regeneration at a molecular level. In the experiments described here, we examined the effect of LV vector-mediated overexpression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) on regeneration of the rat peripheral nerve in a transection/repair model in vivo. We showed that LV vectors can be used to locally elevate levels of NGF and GDNF in the injured rat peripheral nerve and this has profound and differential effects on regenerating sensory and motor neurons. For sensory neurons, increased levels of NGF and GDNF do not affect the number of regenerated neurons 1 cm distal to a lesion at 4 weeks post-lesion but do cause changes in the expression of markers for different populations of nociceptive neurons. These changes are accompanied by significant alterations in the recovery of nociceptive function. For motoneurons, overexpression of GDNF causes trapping of regenerating axons, impairing both long-distance axonal outgrowth and reinnervation of target muscles, whereas NGF has no effect on these parameters. These observations show the feasibility of combining surgical repair of the transected nerve with the application of viral vectors. Furthermore, they show a difference between the regenerative responses of motor and sensory neurons to locally increased levels of NGF and GDNF. SN - 1460-9568 UR - https://www.unboundmedicine.com/medline/citation/18973572/Differential_effects_of_lentiviral_vector_mediated_overexpression_of_nerve_growth_factor_and_glial_cell_line_derived_neurotrophic_factor_on_regenerating_sensory_and_motor_axons_in_the_transected_peripheral_nerve_ L2 - https://doi.org/10.1111/j.1460-9568.2008.06452.x DB - PRIME DP - Unbound Medicine ER -