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

Autor:	Martijn R. Tannemaat, Godard C.W. de Ruiter, G. J. Boer, Martijn J. A. Malessy, Ruben Eggers, Chris W. Pool, Joost Verhaagen, William T. Hendriks, Joop J. van Heerikhuize
Přispěvatelé:	Netherlands Institute for Neuroscience (NIN)
Rok vydání:	2008
Předmět:	Sensory Receptor Cells Genetic Vectors Nerve guidance conduit Wistar Nerve Tissue Proteins Research Support Lesion Neurotrophic factors Peripheral Nerve Injuries Nerve Growth Factor Glial cell line-derived neurotrophic factor medicine Journal Article Animals Comparative Study Glial Cell Line-Derived Neurotrophic Factor Nerve Growth Factors Peripheral Nerves Rats Wistar Non-U.S. Gov't Motor Neurons biology Research Support Non-U.S. Gov't General Neuroscience Regeneration (biology) Lentivirus Nociceptors Peripheral Nervous System Diseases Recovery of Function Axons Nerve Regeneration Rats Up-Regulation Nerve growth factor Nociception medicine.anatomical_structure Treatment Outcome nervous system biology.protein Female medicine.symptom Neuroscience Biomarkers Reinnervation
Zdroj:	The European journal of neuroscience, 28(8), 1467-79. Wiley-Blackwell
ISSN:	1460-9568 0953-816X
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5008cdd4cdbd5ed61c3b6249325da533 https://pubmed.ncbi.nlm.nih.gov/18973572 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.