Journal Article

DZNE-2024-00531

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Transplantation of dorsal root ganglia overexpressing the NaChBac sodium channel improves locomotion after complete SCI

Hingorani, S. ; Paniagua Soriano, G. ; Sánchez Huertas, C. ; Villalba Riquelme, E. M. ; López Mocholi, E. ; Martínez Rojas, B. ; Alastrué Agudo, A. ; Dupraz, S.DZNE* ; Ferrer Montiel, A. V. ; Moreno Manzano, V.

2024
Nature Publ. Group New York, NY

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Please use a persistent id in citations: doi:10.1016/j.ymthe.2024.03.038

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.

Keyword(s): Ganglia, Spinal: metabolism (MeSH) ; Animals (MeSH) ; Spinal Cord Injuries: metabolism (MeSH) ; Spinal Cord Injuries: therapy (MeSH) ; Spinal Cord Injuries: genetics (MeSH) ; Locomotion (MeSH) ; Sodium Channels: metabolism (MeSH) ; Sodium Channels: genetics (MeSH) ; Rats (MeSH) ; Female (MeSH) ; Recovery of Function (MeSH) ; Disease Models, Animal (MeSH) ; Neurons: metabolism (MeSH) ; Mice (MeSH) ; Gene Expression (MeSH) ; Myelin Sheath: metabolism (MeSH) ; Cell Survival (MeSH) ; dorsal root ganglia ; functional recovery ; inhibitory and excitatory input ; neuronal survival ; neuronal transplantation ; sodium channel ; spinal cord injury ; Sodium Channels

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Contributing Institute(s):

1. Axon Growth and Regeneration (AG Bradke)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2024

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; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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