Neurodevelopmental Changes in Excitatory Synaptic Structure and Function in the Cerebral Cortex of Sanfilippo Syndrome IIIA Mice

Overview

Journal Sci Rep

Specialty Science

Date 2017 Apr 19

PMID 28418018

Citations 18

Authors

Chrissa A Dwyer

Samantha L Scudder

Ying Lin

Lara E Dozier

Dustin Phan

Nicola J Allen

Gentry N Patrick

Jeffrey D Esko

Affiliations

Soon will be listed here.

Abstract

Sanfilippo syndrome, MPS IIIA-D, results from deficits in lysosomal enzymes that specifically degrade heparan sulfate, a sulfated glycosaminoglycan. The accumulation of heparan sulfate results in neurological symptoms, culminating in extensive neurodegeneration and early death. To study the impact of storage in postnatal neurodevelopment, we examined murine models of MPS IIIA, which lack the enzyme sulfamidase. We show that changes occur in excitatory postsynaptic structure and function in the somatosensory cortex prior to signs of neurodegeneration. These changes coincide with accumulation of heparan sulfate with characteristic non-reducing ends, which is present at birth in the mutant mice. Accumulation of heparan sulfate was also detected in primary cultures of cortical neural cells, especially astrocytes. Accumulation of heparan sulfate in cultured astrocytes corresponded with augmented extracellular heparan sulfate and glypican 4 levels. Heparan sulfate from the cerebral cortex of MPS IIIA mice showed enhanced ability to increase glutamate AMPA receptor subunits at the cell surface of wild type neurons. These data support the idea that abnormalities in heparan sulfate content and distribution contribute to alterations in postsynaptic function. Our findings identify a disease-induced developmental phenotype that temporally overlaps with the onset of behavioral changes in a mouse model of MPS IIIA.

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References

McLaughlin D, Karlsson F, Tian N, Pratt T, Bullock S, Wilson V . Specific modification of heparan sulphate is required for normal cerebral cortical development. Mech Dev. 2003; 120(12):1481-8. DOI: 10.1016/j.mod.2003.08.008. View

Risher W, Ustunkaya T, Alvarado J, Eroglu C . Rapid Golgi analysis method for efficient and unbiased classification of dendritic spines. PLoS One. 2014; 9(9):e107591. PMC: 4160288. DOI: 10.1371/journal.pone.0107591. View

Lawrence R, Olson S, Steele R, Wang L, Warrior R, Cummings R . Evolutionary differences in glycosaminoglycan fine structure detected by quantitative glycan reductive isotope labeling. J Biol Chem. 2008; 283(48):33674-84. PMC: 2586254. DOI: 10.1074/jbc.M804288200. View

Wilkinson F, Holley R, Langford-Smith K, Badrinath S, Liao A, Langford-Smith A . Neuropathology in mouse models of mucopolysaccharidosis type I, IIIA and IIIB. PLoS One. 2012; 7(4):e35787. PMC: 3338781. DOI: 10.1371/journal.pone.0035787. View

Wijburg F, Wegrzyn G, Burton B, Tylki-Szymanska A . Mucopolysaccharidosis type III (Sanfilippo syndrome) and misdiagnosis of idiopathic developmental delay, attention deficit/hyperactivity disorder or autism spectrum disorder. Acta Paediatr. 2013; 102(5):462-70. PMC: 3654162. DOI: 10.1111/apa.12169. View

Ko J, Pramanik G, Um J, Shim J, Lee D, Kim K . PTPσ functions as a presynaptic receptor for the glypican-4/LRRTM4 complex and is essential for excitatory synaptic transmission. Proc Natl Acad Sci U S A. 2015; 112(6):1874-9. PMC: 4330736. DOI: 10.1073/pnas.1410138112. View

Grobe K, Inatani M, Pallerla S, Castagnola J, Yamaguchi Y, Esko J . Cerebral hypoplasia and craniofacial defects in mice lacking heparan sulfate Ndst1 gene function. Development. 2005; 132(16):3777-86. PMC: 7851831. DOI: 10.1242/dev.01935. View

Ippolito D, Eroglu C . Quantifying synapses: an immunocytochemistry-based assay to quantify synapse number. J Vis Exp. 2010; (45). PMC: 3159596. DOI: 10.3791/2270. View

Lawrence R, Brown J, Al-Mafraji K, Lamanna W, Beitel J, Boons G . Disease-specific non-reducing end carbohydrate biomarkers for mucopolysaccharidoses. Nat Chem Biol. 2012; 8(2):197-204. PMC: 3262053. DOI: 10.1038/nchembio.766. View

10.

Irie F, Badie-Mahdavi H, Yamaguchi Y . Autism-like socio-communicative deficits and stereotypies in mice lacking heparan sulfate. Proc Natl Acad Sci U S A. 2012; 109(13):5052-6. PMC: 3323986. DOI: 10.1073/pnas.1117881109. View

11.

Zhuo L, Theis M, Alvarez-Maya I, Brenner M, Willecke K, Messing A . hGFAP-cre transgenic mice for manipulation of glial and neuronal function in vivo. Genesis. 2001; 31(2):85-94. DOI: 10.1002/gene.10008. View

12.

Lawrence R, Lu H, Rosenberg R, Esko J, Zhang L . Disaccharide structure code for the easy representation of constituent oligosaccharides from glycosaminoglycans. Nat Methods. 2008; 5(4):291-2. DOI: 10.1038/nmeth0408-291. View

13.

Bruyere J, Roy E, Ausseil J, Lemonnier T, Teyre G, Bohl D . Heparan sulfate saccharides modify focal adhesions: implication in mucopolysaccharidosis neuropathophysiology. J Mol Biol. 2014; 427(4):775-791. DOI: 10.1016/j.jmb.2014.09.012. View

14.

Matsumoto Y, Irie F, Inatani M, Tessier-Lavigne M, Yamaguchi Y . Netrin-1/DCC signaling in commissural axon guidance requires cell-autonomous expression of heparan sulfate. J Neurosci. 2007; 27(16):4342-50. PMC: 6672322. DOI: 10.1523/JNEUROSCI.0700-07.2007. View

15.

Vitry S, Ausseil J, Hocquemiller M, Bigou S, dos Santos Coura R, Heard J . Enhanced degradation of synaptophysin by the proteasome in mucopolysaccharidosis type IIIB. Mol Cell Neurosci. 2009; 41(1):8-18. DOI: 10.1016/j.mcn.2009.01.001. View

16.

Bhaumik M, Muller V, Rozaklis T, Johnson L, Dobrenis K, Bhattacharyya R . A mouse model for mucopolysaccharidosis type III A (Sanfilippo syndrome). Glycobiology. 1999; 9(12):1389-96. DOI: 10.1093/glycob/9.12.1389. View

17.

Zhang Y, Chen K, Sloan S, Bennett M, Scholze A, OKeeffe S . An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci. 2014; 34(36):11929-47. PMC: 4152602. DOI: 10.1523/JNEUROSCI.1860-14.2014. View

18.

Dwyer C, Katoh T, Tiemeyer M, Matthews R . Neurons and glia modify receptor protein-tyrosine phosphatase ζ (RPTPζ)/phosphacan with cell-specific O-mannosyl glycans in the developing brain. J Biol Chem. 2015; 290(16):10256-73. PMC: 4400340. DOI: 10.1074/jbc.M114.614099. View

19.

Patrick G, Bingol B, Weld H, Schuman E . Ubiquitin-mediated proteasome activity is required for agonist-induced endocytosis of GluRs. Curr Biol. 2003; 13(23):2073-81. DOI: 10.1016/j.cub.2003.10.028. View

20.

Lawrence R, Brown J, Lorey F, Dickson P, Crawford B, Esko J . Glycan-based biomarkers for mucopolysaccharidoses. Mol Genet Metab. 2013; 111(2):73-83. PMC: 3769472. DOI: 10.1016/j.ymgme.2013.07.016. View