Viral vector-mediated SLC9A6 gene replacement reduces cerebellar dysfunction in the shaker rat model of Christianson syndrome DOI Creative Commons
Collin J. Anderson,

Karla P. Figueroa,

Sharan Paul

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Abstract Background Christianson syndrome (CS) is an x-linked recessive neurodevelopmental and neurodegenerative condition characterized by severe intellectual disability, cerebellar degeneration, ataxia, epilepsy. Mutations to the SLC9A6 gene encoding NHE6 are responsible for CS, we recently demonstrated that a mutation rat Slc9a6 causes similar phenotype in spontaneous shaker model, which exhibits degeneration with motor dysfunction. In previous work, used PhP.eB-L7-Slc9a6-GFP adeno-associated viral (AAV) vector demonstrate replacement Purkinje cells reduced molecular phenotype. Methods We carried out 20-week longitudinal study evaluating impact of cell-specific on ataxia tremor. Taking advantage high homology between human , tested more clinically relevant construct, AAV9-CAG-hSLC9A6 AAV rat. both experimental cohorts, performed studies evaluate expression key markers. then relationship markers function, as well tremor ataxia. Results Administration either or vectors led significant improvement phenotypes. The abundance each disease-relevant proteins was significantly correlated Further, found devolved over time, disease modifying therapy disrupting their temporal relationship. Conclusions These findings future -targeted efforts CS strongly support viable therapeutic strategy. Furthermore, phenotypes may arise from dissociable mechanisms. Graphical

Language: Английский

Unraveling the Neural Signatures: Distinct Pallidal Patterns in Dystonia Subtypes DOI
Alexey Sedov, Indiko Dzhalagoniya, Ulia Semenova

et al.

Parkinsonism & Related Disorders, Journal Year: 2024, Volume and Issue: 130, P. 107207 - 107207

Published: Nov. 29, 2024

Language: Английский

Citations

3
Response -- Letter to the editor: Unraveling the neural signatures: Distinct pallidal patterns in dystonia subtypes DOI
Aasef G. Shaikh,

H. A. Jinnah,

Alexey Sedov

et al.

Parkinsonism & Related Disorders, Journal Year: 2025, Volume and Issue: unknown, P. 107350 - 107350

Published: Feb. 1, 2025

Language: Английский

Citations

0
More Than a Small Brain: The Importance of Studying Neural Function during Development DOI
James C. Dooley, Meike E. van der Heijden

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 44(48), P. e1367242024 - e1367242024

Published: Nov. 27, 2024

The nervous system contains complex circuits comprising thousands of cell types and trillions connections. Here, we discuss how the field “developmental systems neuroscience” combines molecular genetic perspectives developmental neuroscience with (typically adult-focused) functional perspective neuroscience. This combination approaches is critical to understanding a handful cells eventually produce wide range behaviors necessary for survival. Functional circuit development typically lags behind neural connectivity, leading intermediate stages activity that are either not seen in adults or, if present, considered pathophysiological. Developmental examines these activity, mapping out phases inflection points function understand behavior emerge across development. Beyond typical development, this approach provides invaluable insight into pathophysiology neurodevelopmental disorders by identifying when diverges between health disease. We argue will identify important periods reveal novel therapeutic windows treatment, set stage answer fundamental questions about brain

Language: Английский

Citations

0
Viral vector-mediated SLC9A6 gene replacement reduces cerebellar dysfunction in the shaker rat model of Christianson syndrome DOI Creative Commons
Collin J. Anderson,

Karla P. Figueroa,

Sharan Paul

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Abstract Background Christianson syndrome (CS) is an x-linked recessive neurodevelopmental and neurodegenerative condition characterized by severe intellectual disability, cerebellar degeneration, ataxia, epilepsy. Mutations to the SLC9A6 gene encoding NHE6 are responsible for CS, we recently demonstrated that a mutation rat Slc9a6 causes similar phenotype in spontaneous shaker model, which exhibits degeneration with motor dysfunction. In previous work, used PhP.eB-L7-Slc9a6-GFP adeno-associated viral (AAV) vector demonstrate replacement Purkinje cells reduced molecular phenotype. Methods We carried out 20-week longitudinal study evaluating impact of cell-specific on ataxia tremor. Taking advantage high homology between human , tested more clinically relevant construct, AAV9-CAG-hSLC9A6 AAV rat. both experimental cohorts, performed studies evaluate expression key markers. then relationship markers function, as well tremor ataxia. Results Administration either or vectors led significant improvement phenotypes. The abundance each disease-relevant proteins was significantly correlated Further, found devolved over time, disease modifying therapy disrupting their temporal relationship. Conclusions These findings future -targeted efforts CS strongly support viable therapeutic strategy. Furthermore, phenotypes may arise from dissociable mechanisms. Graphical

Language: Английский

Citations

0