Sex differences in gene expression with galactosylceramide treatment in Cln3Δex7/8 mice.

Autor: Makoukji J; Department of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut, Lebanon., El-Sitt S; Department of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut, Lebanon., Makhoul NJ; Department of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut, Lebanon., Soueid J; Department of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut, Lebanon., Kadara H; Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America., Boustany RM; Department of Biochemistry and Molecular Genetics, American University of Beirut Medical Center, Beirut, Lebanon.; Neurogenetics Program, AUBMC Special Kids Clinic and Division of Pediatric Neurology, Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Oct 02; Vol. 15 (10), pp. e0239537. Date of Electronic Publication: 2020 Oct 02 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0239537
Abstrakt: Background: CLN3 disease is caused by mutations in the CLN3 gene. The purpose of this study is to discern global expression patterns reflecting therapeutic targets in CLN3 disease.
Methods: Differential gene expression in vehicle-exposed mouse brain was determined after intraperitoneal vehicle/Galactosylceramide (GalCer) injections for 40 weeks with GeneChip Mouse Genome 430 2.0 arrays.
Results: Analysis identified 66 genes in male and 30 in female brains differentially expressed in GalCer-treated versus vehicle-exposed Cln3Δex7/8 mice. Gene ontology revealed aberrations of biological function including developmental, cellular, and behavioral processes. GalCer treatment altered pathways of long-term potentiation/depression, estrogen signaling, synaptic vesicle cycle, ErbB signaling, and prion diseases in males, but prolactin signaling, selenium compound metabolism and steroid biosynthesis in females. Gene-gene network analysis highlighted networks functionally pertinent to GalCer treatment encompassing motor dysfunction, neurodegeneration, memory disorder, inflammation and astrogliosis in males, and, cataracts, inflammation, astrogliosis, and anxiety in females.
Conclusions: This study sheds light on global expression patterns following GalCer treatment of Cln3Δex7/8 mice. Understanding molecular effects of GalCer on mouse brain gene expression, paves the way for personalized strategies for treating this debilitating disease in humans.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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