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Lentiviral‐mediated silencing of glial fibrillary acidic protein and vimentin promotes anatomical plasticity and functional recovery after spinal cord injury
Author(s) -
Desclaux Mathieu,
Perrin Florence E.,
DoThi Anh,
PrietoCappellini Monica,
Gimenez y Ribotta Minerva,
Mallet Jacques,
Privat Alain
Publication year - 2015
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23468
Subject(s) - glial scar , glial fibrillary acidic protein , astrogliosis , small hairpin rna , regeneration (biology) , spinal cord injury , vimentin , gene silencing , rna interference , spinal cord , microbiology and biotechnology , sprouting , biology , neuroscience , central nervous system , immunology , gene knockdown , rna , cell culture , biochemistry , genetics , immunohistochemistry , botany , gene
In spinal cord injury (SCI), absence of functional recovery and lack of spontaneous axonal regeneration are attributed, among other factors, to the formation of a glial scar that forms both physical and chemical barriers. The glial scar is composed mainly of reactive astrocytes that overexpress two intermediate filament proteins, glial fibrillary acidic protein (GFAP) and vimentin (VIM). To promote regeneration and sprouting of spared axons after spinal cord trauma and with the objective of translation to clinics, we designed an original in vivo gene transfer strategy to reduce glial scar formation after SCI, based on the RNA interference (RNAi)‐mediated inhibition of GFAP and VIM. We first show that direct injection of lentiviral vectors expressing short hairpin RNA (shRNA) against GFAP and VIM in a mouse model of SCI allows efficient and specific targeting of astrocytes. We then demonstrate that the lentiviral‐mediated and stable expression of shGFAP and shVIM leads to a strong reduction of astrogliosis, improves functional motor recovery, and promotes axonal regrowth and sprouting of spared axons. This study thus examplifies how the nonneuronal environment might be a major target within the lesioned central nervous system to promote axonal regeneration (and sprouting) and validates the use of lentiviral‐mediated RNAi in SCI. © 2014 Wiley Periodicals, Inc.