Sortilin is dispensable for secondary injury processes following traumatic brain injury in mice
Issued Date
2024-08-15
Resource Type
ISSN
24058440
Scopus ID
2-s2.0-85199975914
Journal Title
Heliyon
Volume
10
Issue
15
Rights Holder(s)
SCOPUS
Bibliographic Citation
Heliyon Vol.10 No.15 (2024)
Suggested Citation
Staib-Lasarzik I., Gölz C., Bobkiewiecz W., Somnuke P., Sebastiani A., Thal S.C., Schäfer M.K.E. Sortilin is dispensable for secondary injury processes following traumatic brain injury in mice. Heliyon Vol.10 No.15 (2024). doi:10.1016/j.heliyon.2024.e35198 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/100259
Title
Sortilin is dispensable for secondary injury processes following traumatic brain injury in mice
Corresponding Author(s)
Other Contributor(s)
Abstract
Traumatic brain injury (TBI) is characterized by complex secondary injury processes involving the p75 neurotrophin receptor (p75NTR), which has been proposed as a possible therapeutic target. However, the pathogenic role of the p75NTR co-receptor sortilin in TBI has not been investigated. In this study, we examined whether sortilin contributes to acute and early processes of secondary injury using a murine controlled cortical impact (CCI) model of TBI. Initial expression analysis showed a down-regulation of sortilin mRNA levels 1 and 5 day post injury (dpi) and a reduced expression of sortilin protein 1 dpi. Next, a total of 40 SortilinΔExon14 loss-of-function mouse mutants (Sort1−/−) and wild-type (Sort1+/+) littermate mice were subjected to CCI and examined at 1 and 5 dpi. Neither sensorimotor deficits or brain lesion size nor CCI-induced cell death or calcium-dependent excitotoxicity as evaluated by TUNEL staining or Western blot analysis of alpha II spectrin breakdown products were different between Sort1−/− and Sort1+/+ mice. In addition, CCI induced the up-regulation of pro-inflammatory marker mRNA expression (Il6, Tnfa, Aif1, and Gfap) irrespectively of the genotype. Similarly, the mRNA expressions of neurotrophins (Bdnf, Ngf, Nt3), VPS10P domain receptors others than sortilin (Ngfr, Sorl1, Sorcs2), and the sortilin interactor progranulin were not affected by genotype. Our results suggest that sortilin is a modulatory rather than a critical factor in the acute and early brain tissue response after TBI.