Sialylation regulates brain structure and function

Seung Wan Yoo, Mary G. Motari, Keiichiro Susuki, Jillian Prendergast, Andrea Mountney, Andres Hurtado, Ronald L. Schnaar

Research output: Contribution to journalArticlepeer-review

Abstract

Every cell expresses a molecularly diverse surface glycan coat (glycocalyx) comprising its interface with its cellular environment. In vertebrates, the terminal sugars of the glycocalyx are often sialic acids, 9-carbon backbone anionic sugars implicated in intermolecular and intercellular interactions. The vertebrate brain is particularly enriched in sialic acid-containing glycolipids termed gangliosides. Human congenital disorders of ganglioside biosynthesis result in paraplegia, epilepsy, and intellectual disability. To better understand sialoglycan functions in the nervous system, we studied brain anatomy, histology, biochemistry, and behavior inmice with engineeredmutations in St3gal2 and St3gal3, sialyltransferase genes responsible for terminal sialylation of gangliosides and some glycoproteins. St3gal2/3 double-null mice displayed dysmyelination marked by a 40% reduction in major myelin proteins, 30% fewer myelinated axons, a 33% decrease in myelin thickness, and molecular disruptions at nodes of Ranvier. In part, these changes may be due to dysregulation of ganglioside-mediated oligodendroglial precursor cell proliferation. Neuronal markers were also reduced up to 40%, and hippocampal neurons had smaller dendritic arbors. Young adult St3gal2/3 double-nullmice displayed impaired motor coordination, disturbed gait, and profound cognitive disability. Comparisons among sialyltransferase mutant mice provide insights into the functional roles of brain gangliosides and sialoglycoproteins consistent with related human congenital disorders.

Original languageEnglish (US)
Pages (from-to)3040-3053
Number of pages14
JournalFASEB Journal
Volume29
Issue number7
DOIs
StatePublished - Jul 1 2015

Keywords

  • Animal models
  • Behavior
  • Gangliosides
  • Myelin
  • Oligodendrocyte precursor cells

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint

Dive into the research topics of 'Sialylation regulates brain structure and function'. Together they form a unique fingerprint.

Cite this