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Article: ASD-like behaviors, a dysregulated inflammatory response and decreased expression of PLP1 characterize mice deficient for sialyltransferase ST3GAL5

TitleASD-like behaviors, a dysregulated inflammatory response and decreased expression of PLP1 characterize mice deficient for sialyltransferase ST3GAL5
Authors
KeywordsLactosylceramide alpha-2,3-sialyltransferase (ST3GAL5)
Major brain gangliosides
Autism spectrum disorder (ASD)
Aggression
Proteolipid protein 1 (Plp1)
Neuroinflammation
Mice
Issue Date2021
PublisherElsevier Inc. The Journal's web site is located at https://www.journals.elsevier.com/brain-behavior-and-immunity-health
Citation
Brain, Behavior, & Immunity - Health, 2021, v. 16, article no. 100306 How to Cite?
AbstractGangliosides are glycosphingolipids, which are abundant in brain, are known to modulate ion channels and cell-to-cell communication. Deficiencies can result in aberrant myelination and altered immune responses, which can give rise to neurodevelopmental psychiatric disorders. However, to date, little mechanistic data is available on how ganglioside deficiencies contribute to the behavioural disorders. In humans, the loss of lactosylceramide-alpha-2,3-sialyltransferase (ST3Gal5) leads to a severe neuropathology, but in ST3Gal5 knock-out (St3gal5−/−) mice the absence of GM3 and associated a-, b- and c-series gangliosides is partially compensated by 0-series gangliosides and there is no overt behavioural phenotype. Here, we sought to examine the behavioural and molecular consequences of GM3 loss more closely. Mutants of both sexes exhibited impaired conditioned taste aversion in an inhibitory learning task and anxiety-like behaviours in the open field, moderate motor deficits, abnormal social interactions, excessive grooming and rearing behaviours. Taken together, the aberrant behaviours are suggestive of an autism spectrum disorder (ASD)-like syndrome. Molecular analysis showed decreased gene and protein expression of proteolipid protein-1 (Plp1) and over expression of proinflammatory cytokines, which has been associated with ASD-like syndromes. The inflammatory and behavioural responses to lipopolysaccharide (LPS) were also altered in the St3gal5−/− mice compared to wild-type, which is indicative of the importance of GM3 gangliosides in regulating immune responses. Together, the St3gal5−/− mice display ASD-like behavioural features, altered response to systemic inflammation, signs of hypomyelination and neuroinflammation, which suggests that deficiency in a- and b-series gangliosides could contribute to the development of an ASD-like pathology in humans.
Persistent Identifierhttp://hdl.handle.net/10722/301614
ISSN
2023 Impact Factor: 3.7
2023 SCImago Journal Rankings: 1.235
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorStrekalova, T-
dc.contributor.authorSvirin, E-
dc.contributor.authorVeniaminova, E-
dc.contributor.authorKopeikina, E-
dc.contributor.authorVeremeyko, T-
dc.contributor.authorYung, AWY-
dc.contributor.authorProshin, A-
dc.contributor.authorWalitza, S-
dc.contributor.authorAnthony, DC-
dc.contributor.authorLim, LW-
dc.contributor.authorLesch, KP-
dc.contributor.authorPonomarev, ED-
dc.date.accessioned2021-08-09T03:41:38Z-
dc.date.available2021-08-09T03:41:38Z-
dc.date.issued2021-
dc.identifier.citationBrain, Behavior, & Immunity - Health, 2021, v. 16, article no. 100306-
dc.identifier.issn2666-3546-
dc.identifier.urihttp://hdl.handle.net/10722/301614-
dc.description.abstractGangliosides are glycosphingolipids, which are abundant in brain, are known to modulate ion channels and cell-to-cell communication. Deficiencies can result in aberrant myelination and altered immune responses, which can give rise to neurodevelopmental psychiatric disorders. However, to date, little mechanistic data is available on how ganglioside deficiencies contribute to the behavioural disorders. In humans, the loss of lactosylceramide-alpha-2,3-sialyltransferase (ST3Gal5) leads to a severe neuropathology, but in ST3Gal5 knock-out (St3gal5−/−) mice the absence of GM3 and associated a-, b- and c-series gangliosides is partially compensated by 0-series gangliosides and there is no overt behavioural phenotype. Here, we sought to examine the behavioural and molecular consequences of GM3 loss more closely. Mutants of both sexes exhibited impaired conditioned taste aversion in an inhibitory learning task and anxiety-like behaviours in the open field, moderate motor deficits, abnormal social interactions, excessive grooming and rearing behaviours. Taken together, the aberrant behaviours are suggestive of an autism spectrum disorder (ASD)-like syndrome. Molecular analysis showed decreased gene and protein expression of proteolipid protein-1 (Plp1) and over expression of proinflammatory cytokines, which has been associated with ASD-like syndromes. The inflammatory and behavioural responses to lipopolysaccharide (LPS) were also altered in the St3gal5−/− mice compared to wild-type, which is indicative of the importance of GM3 gangliosides in regulating immune responses. Together, the St3gal5−/− mice display ASD-like behavioural features, altered response to systemic inflammation, signs of hypomyelination and neuroinflammation, which suggests that deficiency in a- and b-series gangliosides could contribute to the development of an ASD-like pathology in humans.-
dc.languageeng-
dc.publisherElsevier Inc. The Journal's web site is located at https://www.journals.elsevier.com/brain-behavior-and-immunity-health-
dc.relation.ispartofBrain, Behavior, & Immunity - Health-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectLactosylceramide alpha-2,3-sialyltransferase (ST3GAL5)-
dc.subjectMajor brain gangliosides-
dc.subjectAutism spectrum disorder (ASD)-
dc.subjectAggression-
dc.subjectProteolipid protein 1 (Plp1)-
dc.subjectNeuroinflammation-
dc.subjectMice-
dc.titleASD-like behaviors, a dysregulated inflammatory response and decreased expression of PLP1 characterize mice deficient for sialyltransferase ST3GAL5-
dc.typeArticle-
dc.identifier.emailLim, LW: limlw@hku.hk-
dc.identifier.authorityLim, LW=rp02088-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.bbih.2021.100306-
dc.identifier.pmid34589798-
dc.identifier.pmcidPMC8474501-
dc.identifier.hkuros324008-
dc.identifier.volume16-
dc.identifier.spagearticle no. 100306-
dc.identifier.epagearticle no. 100306-
dc.publisher.placeUnited States-

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