Bibliographic Details
| Title: |
AAV6 mediated Gsx1 expression in neural stem progenitor cells promotes neurogenesis and restores locomotor function after contusion spinal cord injury |
| Authors: |
Zachary Finkel, Fatima Esteban, Brianna Rodriguez, Tanner Clifford, Adelina Joseph, Hani Alostaz, Mridul Dalmia, Juan Gutierrez, Matthew J. Tamasi, Samuel Ming Zhang, Jonah Simone, Hafize Petekci, Susmita Nath, Miriam Escott, Shivam Kumar Garg, Adam J. Gormley, Suneel Kumar, Sonia Gulati, Li Cai |
| Source: |
Neurotherapeutics, Vol 21, Iss 4, Pp e00362- (2024) |
| Publisher Information: |
Elsevier, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Neurology. Diseases of the nervous system |
| Subject Terms: |
Genomic screened homeobox 1 (Gsh1 or Gsx1), Gene therapy, Neural stem/progenitor cell, Neurogenesis, Neural regeneration, Traumatic spinal cord injury, Neurology. Diseases of the nervous system, RC346-429 |
| More Details: |
Genomic screened homeobox 1 (Gsx1 or Gsh1) is a neurogenic transcription factor required for the generation of excitatory and inhibitory interneurons during spinal cord development. In the adult, lentivirus (LV) mediated Gsx1 expression promotes neural regeneration and functional locomotor recovery in a mouse model of lateral hemisection spinal cord injury (SCI). The LV delivery method is clinically unsafe due to insertional mutations to the host DNA. In addition, the most common clinical case of SCI is contusion/compression. In this study, we identify that adeno-associated virus serotype 6 (AAV6) preferentially infects neural stem/progenitor cells (NSPCs) in the injured spinal cord. Using a rat model of contusion SCI, we demonstrate that AAV6 mediated Gsx1 expression promotes neurogenesis, increases the number of neuroblasts/immature neurons, restores excitatory/inhibitory neuron balance and serotonergic neuronal activity through the lesion core, and promotes locomotor functional recovery. Our findings support that AAV6 preferentially targets NSPCs for gene delivery and confirmed Gsx1 efficacy in clinically relevant rat model of contusion SCI. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1878-7479 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S1878747924000485; https://doaj.org/toc/1878-7479 |
| DOI: |
10.1016/j.neurot.2024.e00362 |
| Access URL: |
https://doaj.org/article/f01b4eae704842cea72b577e97bd7cfd |
| Accession Number: |
edsdoj.f01b4eae704842cea72b577e97bd7cfd |
| Database: |
Directory of Open Access Journals |
Full Text from SpringerLink