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@ARTICLE{Hingorani:269434,
author = {Hingorani, Sonia and Paniagua Soriano, Guillem and Sánchez
Huertas, Carlos and Villalba Riquelme, Eva María and López
Mocholi, Eric and Martínez Rojas, Beatriz and Alastrué
Agudo, Ana and Dupraz, Sebastián and Ferrer Montiel,
Antonio Vicente and Moreno Manzano, Victoria},
title = {{T}ransplantation of dorsal root ganglia overexpressing the
{N}a{C}h{B}ac sodium channel improves locomotion after
complete {SCI}},
journal = {Molecular therapy},
volume = {32},
number = {6},
issn = {1525-0016},
address = {New York, NY},
publisher = {Nature Publ. Group},
reportid = {DZNE-2024-00531},
pages = {1739 - 1759},
year = {2024},
abstract = {Spinal cord injury (SCI) is a debilitating condition
currently lacking treatment. Severe SCI causes the loss of
most supraspinal inputs and neuronal activity caudal to the
injury, which, coupled with the limited endogenous capacity
for spontaneous regeneration, can lead to complete
functional loss even in anatomically incomplete lesions. We
hypothesized that transplantation of mature dorsal root
ganglia (DRGs) genetically modified to express the NaChBac
sodium channel could serve as a therapeutic option for
functionally complete SCI. We found that NaChBac expression
increased the intrinsic excitability of DRG neurons and
promoted cell survival and neurotrophic factor secretion in
vitro. Transplantation of NaChBac-expressing dissociated
DRGs improved voluntary locomotion 7 weeks after injury
compared to control groups. Animals transplanted with
NaChBac-expressing DRGs also possessed higher
tubulin-positive neuronal fiber and myelin preservation,
although serotonergic descending fibers remained unaffected.
We observed early preservation of the corticospinal tract 14
days after injury and transplantation, which was lost 7
weeks after injury. Nevertheless, transplantation of
NaChBac-expressing DRGs increased the neuronal excitatory
input by an increased number of VGLUT2 contacts immediately
caudal to the injury. Our work suggests that the
transplantation of NaChBac-expressing dissociated DRGs can
rescue significant motor function, retaining an excitatory
neuronal relay activity immediately caudal to injury.},
keywords = {Ganglia, Spinal: metabolism / Animals / Spinal Cord
Injuries: metabolism / Spinal Cord Injuries: therapy /
Spinal Cord Injuries: genetics / Locomotion / Sodium
Channels: metabolism / Sodium Channels: genetics / Rats /
Female / Recovery of Function / Disease Models, Animal /
Neurons: metabolism / Mice / Gene Expression / Myelin
Sheath: metabolism / Cell Survival / dorsal root ganglia
(Other) / functional recovery (Other) / inhibitory and
excitatory input (Other) / neuronal survival (Other) /
neuronal transplantation (Other) / sodium channel (Other) /
spinal cord injury (Other) / Sodium Channels (NLM
Chemicals)},
cin = {AG Bradke},
ddc = {610},
cid = {I:(DE-2719)1013002},
pnm = {351 - Brain Function (POF4-351)},
pid = {G:(DE-HGF)POF4-351},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC11184342},
pubmed = {pmid:38556794},
doi = {10.1016/j.ymthe.2024.03.038},
url = {https://pub.dzne.de/record/269434},
}