TY  - JOUR
AU  - Hingorani, Sonia
AU  - Paniagua Soriano, Guillem
AU  - Sánchez Huertas, Carlos
AU  - Villalba Riquelme, Eva María
AU  - López Mocholi, Eric
AU  - Martínez Rojas, Beatriz
AU  - Alastrué Agudo, Ana
AU  - Dupraz, Sebastián
AU  - Ferrer Montiel, Antonio Vicente
AU  - Moreno Manzano, Victoria
TI  - Transplantation of dorsal root ganglia overexpressing the NaChBac sodium channel improves locomotion after complete SCI
JO  - Molecular therapy
VL  - 32
IS  - 6
SN  - 1525-0016
CY  - New York, NY
PB  - Nature Publ. Group
M1  - DZNE-2024-00531
SP  - 1739 - 1759
PY  - 2024
AB  - 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.
KW  - Ganglia, Spinal: metabolism
KW  - Animals
KW  - Spinal Cord Injuries: metabolism
KW  - Spinal Cord Injuries: therapy
KW  - Spinal Cord Injuries: genetics
KW  - Locomotion
KW  - Sodium Channels: metabolism
KW  - Sodium Channels: genetics
KW  - Rats
KW  - Female
KW  - Recovery of Function
KW  - Disease Models, Animal
KW  - Neurons: metabolism
KW  - Mice
KW  - Gene Expression
KW  - Myelin Sheath: metabolism
KW  - Cell Survival
KW  - dorsal root ganglia (Other)
KW  - functional recovery (Other)
KW  - inhibitory and excitatory input (Other)
KW  - neuronal survival (Other)
KW  - neuronal transplantation (Other)
KW  - sodium channel (Other)
KW  - spinal cord injury (Other)
KW  - Sodium Channels (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC11184342
C6  - pmid:38556794
DO  - DOI:10.1016/j.ymthe.2024.03.038
UR  - https://pub.dzne.de/record/269434
ER  -