Naslov
Brain lipidomics of St8sia1 knockout mouse predicts neurological deficit

Autori
Grbavac, Josip ; Zjalić, Milorad ; Debeljak, Željko ; Mandić, Dario ; Heffer, Marija

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

ISBN
970-615-6006-03-5

Skup
4th RECOOP International Student and 17th RECOOP Bridges in Life Sciences Annual Conferences

Mjesto i datum
Prag, Češka Republika, 06.04.2022. - 09.04.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
St8sia1, lipidomics, MALDI-TOF-MS, gangliosides, GD3 synthase

Sažetak
Introduction: Gangliosides are major constituents of plasma membrane signaling domains - lipid rafts. St8sia1 knockout mice lack b-series ganglioside synthesis (GD1b and GT1b) which is compensated by increased a-series ganglioside synthesis (GM1 and GD1a) but does not lead to changes in brain morphology. Materials and methods: MALDI-TOF-MS analysis of fresh brain tissue was performed on St8sia1 knockout (KO) mice 4.5 months old and wild-type controls (WT). To determine relevant molecular differences between the groups, the significance level was set to 0.05 and the statistical analysis was performed using ANOVA with Bonferroni correction. Succinate dehydrogenase enzyme activity was shown by histological staining. Tissue distribution of cholesterol, phospholipids, and actin was determined by fluorescent assays (TopFluor Cholesterol, Sulforhodamine, and Rhodamine Phalloidin, respectively). Histological staining was quantified using a computer program Fiji. Results: The principal component analysis of lipidomic data showed a clear separation between KO and WT - PC1 and PC2 explained 87.25% of the variability. A statistically significant downregulation in basal ganglia of KO animals was found in metabolites of the following synthetic pathways: porphyrins, ubiquinone, ferroptosis, and fat chain elongation. The sensitivity of their basal ganglia to oxidative damage and ferroptosis is further supported by the finding of reduced succinate dehydrogenase activity. Additionally, weaker cholesterol and phospholipid staining was found throughout capsula interna, nucleus caudatus and putamen of KO animals. Contrary, actin microfilament staining was significantly enhanced in examined brain regions of KO mice which could indicate amplified axon growth. Discussion and conclusion: Deficiency in ganglioside synthesis in St8sia KO mice leads to a number of metabolic adjustments. Subsequent studies should demonstrate the resistance of the oxidative-reductive balance in the basal ganglia to minor insults. Clinical aplication: Every cell in nature carries a rich surface coat of glycans, its glycocalyx. Among their functions, gangliosides regulate cell- cell interactions and modulate the activities of other cell surface molecules. Some studies have shown a strong correlation between the malignancy in mice model gliomas and the expression of the St8sia1 gene. Also, a clear correlation is seen in the role of adult brain plasticity, including regeneration, with the ganglioside composition. It is yet uncertain how this finding could benefit the standard clinical practice.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

Napomena
Support: Croatian Science Foundation under project
number 2158-61-
07-14-118 and European regional development and
Croatian Ministry of Science fund under
project number KK.01.1.1.02.0015.

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