Transcriptomic analysis reinforces the implication of spatacsin in neuroinflammation and neurodevelopment

Liriopé Toupenet Marchesi, Daniel Stockholm, Typhaine Esteves, Marion Leblanc, Nicolas Auger, Julien Branchu, Khalid Hamid El Hachimi, Giovanni Stevanin
Scientific Reports. 2025-01-18; 15(1):
DOI: 10.1038/s41598-025-86337-9

1. Sci Rep. 2025 Jan 18;15(1):2370. doi: 10.1038/s41598-025-86337-9.

Transcriptomic analysis reinforces the implication of spatacsin in
neuroinflammation and neurodevelopment.

Toupenet Marchesi L(1)(2), Stockholm D(2)(3), Esteves T(1)(2), Leblanc M(1)(2),
Auger N(1)(2), Branchu J(1), El Hachimi KH(1)(2), Stevanin G(4)(5).

Author information:
(1)Paris Brain Institute (ICM), Sorbonne University, INSERM, CNRS, APHP, Paris,
France.
(2)PSL Research University, EPHE, Paris, France.
(3)Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, Paris,
France.
(4)PSL Research University, EPHE, Paris, France. .
(5)Institut des Neurosciences cognitives et intégratives d’Aquitaine (INCIA),
Bordeaux University, CNRS, Bordeaux, France. .

Hereditary spastic paraplegia (HSP) encompasses a group of rare genetic diseases
primarily affecting motor neurons. Among these, spastic paraplegia type 11
(SPG11) represents a complex form of HSP caused by deleterious variants in the
SPG11 gene, which encodes the spatacsin protein. Previous studies have described
several potential roles for spatacsin, including its involvement in lysosome and
autophagy mechanisms, neuronal and neurites development or mitochondria
function. Despite these findings, the precise function of the spatacsin protein
remains elusive. To elucidate its function, we conducted an extensive RNA
sequencing (RNAseq) experiment and transcriptomic analysis in three distinct
neural structures (cerebellum, cortex and hippocampus) and at three different
ages (6 weeks, 4 months and 8 months) in both wild type and Spg11-/- mice. Our
functional analysis of differentially expressed genes (DEGs) and Gene Set
Enrichment Analysis (GSEA) revealed dysregulation in pathways related to
inflammation, RNA metabolism and neuronal and neurite development, factors
frequently implicated in neurodegenerative disorders. Notably, we also observed
early deregulation in cellular pathways related to cell proliferation. Our
results represent a significant step towards a better understanding of the
functions of spatacsin in the cell and the underlying cellular mechanisms
disrupted by its absence.

DOI: 10.1038/s41598-025-86337-9
PMCID: PMC11743199
PMID: 39827309 [Indexed for MEDLINE]

Conflict of interest statement: Declarations. Competing interests: The authors
declare no competing interests. Ethics: This work was performed on RNA from mice
according to the agreement of the Ethic Committee “Charles Darwin” n°
Ce5/2012/045 and mouse handling was performed by trained biologists as required
by the law.