Abstract:
:The retrograde axonal transport mechanism of motor neurons has been exploited to deliver the gene encoding Glial cell line-derived neurotrophic factor (GDNF) into the central nervous system to provide trophic support following injury. A nonviral gene delivery system, consisting of a monoclonal antibody (MC192) that binds the neurotrophic receptor, p75(NTR), coupled to poly-L-lysine, was constructed and used to deliver the gene via a receptor-mediated mechanism. The MC192-poly-l-lysine/pGDNF complex was injected into the hind limb of newborn rats to allow gene expression within motor neurons prior to sciatic nerve transection. In adult rats, the gene delivery complex was administrated in gel foam placed on a transected hypoglossal nerve. We show that the delivered construct is internalized following binding to p75(NTR) and is transported into the brain and spinal cord, bypassing the blood-brain barrier. The presence of the GDNF transgene and its transcript could be detected for up to 8 weeks in spinal cord and brain stem. Expression of the GDNF protein rescued 38% of the targeted motor neurons 1 week postinjury in newborn rats while the survival rate in control group was below 12%. In adult rats, neuronal death induced by axotomy was almost completely reversed by the introduction of the transgene (95 +/- 3%). Thus, the significant functional outcomes of this novel gene delivery system are demonstrated both in postnatal and adult motor neurons.
journal_name
Exp Neuroljournal_title
Experimental neurologyauthors
Barati S,Hurtado PR,Zhang SH,Tinsley R,Ferguson IA,Rush RAdoi
10.1016/j.expneurol.2006.05.027subject
Has Abstractpub_date
2006-11-01 00:00:00pages
179-88issue
1eissn
0014-4886issn
1090-2430pii
S0014-4886(06)00331-1journal_volume
202pub_type
杂志文章abstract::The monoclonal antibody Py has previously been shown to be a useful marker for subpopulations of neurons in the rat brain. However, the distribution of Py immunoreactivity in other regions of the CNS and PNS is not known. Here, we present a light and electron microscopic investigation into the distribution of Py immun...
journal_title:Experimental neurology
pub_type: 杂志文章
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journal_title:Experimental neurology
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journal_title:Experimental neurology
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journal_title:Experimental neurology
pub_type: 杂志文章
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journal_title:Experimental neurology
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pub_type: 杂志文章
doi:10.1016/0014-4886(83)90278-9
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journal_title:Experimental neurology
pub_type: 杂志文章
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journal_title:Experimental neurology
pub_type: 杂志文章,评审
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更新日期:1992-01-01 00:00:00
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journal_title:Experimental neurology
pub_type: 杂志文章
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journal_title:Experimental neurology
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journal_title:Experimental neurology
pub_type: 杂志文章
doi:10.1016/j.expneurol.2008.08.013
更新日期:2008-12-01 00:00:00