Journal article
Activity of spinal RORβ neurons is related to functional improvements following combination treatment after complete SCI
Proceedings of the National Academy of Sciences - PNAS, v 122(15), e2406333122
15 Apr 2025
PMID: 40198697
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Various strategies targeting spinal locomotor circuitry have been associated with functional improvements after spinal cord injury (SCI). However, the neuronal populations mediating beneficial effects remain largely unknown. Using a combination therapy in a mouse model of complete SCI, we show that virally delivered brain-derived neurotrophic factor (BDNF) (AAV-BDNF) activates hindlimb stepping and causes hyperreflexia, whereas submotor threshold epidural stimulation (ES) reduces BDNF-induced hyperreflexia. Given their role in gating proprioceptive afferents and as a potential convergence point of BDNF and ES, we hypothesized that an enhanced excitability of inhibitory RORβ neurons would be associated with locomotor improvements. Ex vivo spinal slice recordings from mice with a range of locomotor and hyperreflexia scores revealed that the excitability of RORβ neurons was related to functional outcome post-SCI. Mice with poor locomotor function after SCI had less excitable RORβ neurons, but the excitability of RORβ neurons was similar between the uninjured and "best stepping" SCI groups. Further, chemogenetic activation of RORβ neurons reduced BDNF-induced hyperreflexia and improved stepping, similar to ES. Our findings identify inhibitory RORβ neurons as a target population to limit hyperreflexia and enhance locomotor function after SCI.
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Details
- Title
- Activity of spinal RORβ neurons is related to functional improvements following combination treatment after complete SCI
- Creators
- Nicholas J Stachowski - Drexel UniversityJaimena H Wheel - Drexel UniversityShayna Singh - Drexel UniversitySebastian J Atoche - Drexel UniversityLihua Yao - Drexel UniversityD Leonardo Garcia-Ramirez - Drexel UniversitySimon F Giszter - Drexel UniversityKimberly J Dougherty - Drexel University
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 122(15), e2406333122
- Publisher
- NATL ACAD SCIENCES
- Number of pages
- 12
- Grant note
- NS132514 / HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS) NS127584 / HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS) NS104194 / HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS) NS130799 / HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:001471196000001
- Scopus ID
- 2-s2.0-105002744541
- Other Identifier
- 991022047146904721
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- Web of Science research areas
- Neurosciences