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Article ; Online: AAV6 mediated Gsx1 expression in neural stem progenitor cells promotes neurogenesis and restores locomotor function after contusion spinal cord injury.

Finkel, Zachary / Esteban, Fatima / Rodriguez, Brianna / Clifford, Tanner / Joseph, Adelina / Alostaz, Hani / Dalmia, Mridul / Gutierrez, Juan / Tamasi, Matthew J / Zhang, Samuel Ming / Simone, Jonah / Petekci, Hafize / Nath, Susmita / Escott, Miriam / Garg, Shivam Kumar / Gormley, Adam J / Kumar, Suneel / Gulati, Sonia / Cai, Li

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics

2024  , Page(s) e00362

Abstract: 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 ... ...

Abstract 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.
Language English
Publishing date 2024-04-24
Publishing country United States
Document type Journal Article
ZDB-ID 2316693-9
ISSN 1878-7479 ; 1933-7213
ISSN (online) 1878-7479
ISSN 1933-7213
DOI 10.1016/j.neurot.2024.e00362
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Zs.A 6156: Show issues Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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ab Jg. 2022: Lesesaal (EG)

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