Deficiency in ß-galactoside alpha-2,3-sialyltransferase 5 gene results in significant neuronal damage and cognitive decline after traumatic brain injury
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AbstractBrain glycosphingolipids, also called gangliosides, within neuronal lipid rafts (NLR) induce platelet degranulation and the secretion of neurotransmitters and pro-inflammatory agents. Traumatic brain injury (TBI) is associated with the extravasation of platelets, which can contribute to inflammation and neurodegeneration. Here, we compared the outcome of TBI in wild-type and glycosphingolipid-deficient animals. The St3gal5 gene encodes for ST3 ß-galactoside alpha-2,3-sialyltransferase 5, which is responsible for biosynthesis of complex a- and b-series gangliosides. We found that uninjured St3gal5-deficient mice exhibit normal cognitive and social behaviours, but do exhibit some mild motor deficits. After traumatic brain injury (TBI) St3gal5-deficient animals exhibit marked deficits in cognitive and motor functions, which was associated with increased haemorrhage and neuronal damage owing to the failure of NLR-induced platelet serotonin (5-HT) release. Decrease in NLR-induced platelet-derived platelet activating factor (PAF) release also resulted in reduced microglial activation and central nervous system macrophage infiltration in the St3gal5-deficient animals after TBI. Further investigation demonstrated that the interaction of platelets with NLR stimulates neurite growth, increased the number of dendritic spines, and increased neuronal activity. Our study establishes an important role for major brain glycolipids and platelet-derived factors in the regulation of neuroinflammation, haemorrhage and neuronal plasticity after brain injury.
Acceptance Date15/04/2019
All Author(s) ListDukhinova M., Kopeikina E., Vermeyko T., Yung A.W.Y., Ponomarev E.
Name of ConferenceGordon Research Conference: Cognitive Dysfunction in Brain Diseases Gordon Research Conference
Start Date of Conference12/05/2019
End Date of Conference17/05/2019
Place of ConferenceShatin
Country/Region of ConferenceHong Kong
LanguagesEnglish-United Kingdom
KeywordsGangliosides, cognitive problems, TBI

Last updated on 2019-21-05 at 16:29