Divergent impact of the polysialyltransferases ST8SiaII and ST8SiaIV on polysialic acid expression in immature neurons and interneurons of the adult cerebral cortex

doi:10.1016/j.neuroscience.2010.02.067

Neuroscience

Volume 167, Issue 3, 19 May 2010, Pages 825-837

https://doi.org/10.1016/j.neuroscience.2010.02.067 Get rights and content

Abstract

Polysialic acid (PSA) is a negatively charged carbohydrate polymer, which confers antiadhesive properties to the neural cell adhesion molecule NCAM and facilitates cellular plasticity during brain development. In mice, PSA expression decreases drastically during the first postnatal weeks and it gets confined to immature neurons and regions displaying structural plasticity during adulthood. In the brain, PSA is exclusively synthesized by the two polysialyltransferases ST8SiaII and ST8SiaIV. To study their individual contribution to polysialylation in the adult, we analyzed PSA expression in mice deficient for either polysialyltransferase. Focusing on the cerebral cortex, our results indicate that ST8SiaIV is solely responsible for PSA expression in mature interneurons and in most regions of cortical neuropil. By contrast, ST8SiaII is the major polysialyltransferase in immature neurons of the paleocortex layer II and the hippocampal subgranular zone. The numbers of cells expressing PSA or doublecortin, another marker of immature neurons, were increased in the paleocortex layer II of ST8SiaIV-deficient mice, indicating altered differentiation of these cells. Analysis of doublecortin expression also indicated that the production of new granule neurons in the subgranular zone of ST8SiaII-deficient mice is not affected. However, many of the immature granule neurons showed aberrant locations and morphology, suggesting a role of ST8SiaII in their terminal differentiation.

Section snippets

Experimental procedures

St8siaII and St8siaIV knock out strains (Eckhardt et al., 2000, Angata et al., 2004) were backcrossed with C57BL/6J mice for six generations and mice heterozygous for the mutant polysialyltransferase alleles were interbred to obtain wildtype or knockout offspring (St8siaII^−/−, St8siaIV^−/−). Of each genotype, five males at the age of 3 month were used in this study. All animal experimentation was conducted in accordance with the European Communities Council Directive of November 24, 1986

Neocortex

In wild type animals PSA expressing cells and PSA-positive neuropil were detected in all regions of the neocortex. As exemplarily shown for the cingulate cortex (Figs. 1A and 2A), PSA-positive cells were particularly abundant in deep layers. Similar to the situation in adult rats (Varea et al., 2005, Varea et al., 2007a) many of the PSA-positive cells displayed multipolar morphologies and neuropil staining was generally more intense in deep layers, specially in the infralimbic and prelimbic

Discussion

The comparative immunohistochemical analysis of residual PSA expression in mice lacking either of the two polysialyltransferases, ST8SiaII or ST8SiaIV, provides a detailed picture of the divergent impact of the two enzymes across different regions of the mature mouse forebrain. In overview, the data demonstrate that both polysialyltransferases contribute to PSA synthesis in the mature brain but their share is clearly different. As assessed before by real time RT-PCR and Western blot analyses of

Acknowledgments

Deutsche ForschungsgemeinschaftDFGHi678/4-1 to H.H. Spanish Ministry of Science and Innovation (MICINN-FEDER)BFU2006-07313/BFI and BFU2009-12284/BFI, Generalitat ValencianaCS2009-AP-127 and ACOMP2009/271 to J.N.; Guirado R. has a FPI predoctoral fellowship from the Spanish Ministry of Education and Science (BES 2007-15757).

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In the nervous system, polysialic acid (PSA), a polymer of α2,8-linked sialic acids (Finne, 1982), is predominantly carried by NCAM in its extracellular domain. PSA contributes to regulation of cell interactions during ontogenetic development and affects synaptic activities and regeneration after trauma in the adult nervous system (Eckhardt et al., 2000; Angata et al., 2004; Dityatev et al., 2004; Kleene and Schachner, 2004; Rutishauser, 2008; Bonfanti and Theodosis, 2009; Mühlenhoff et al., 2009; El Maarouf and Rutishauser, 2010; Gascon et al., 2010; Hildebrandt et al., 2010; Kochlamazashvili et al., 2010; Nacher et al., 2010; Schiff et al., 2011). PSA not only modulates the functions of NCAM indirectly but also directly influences cellular features by binding to histone H1, brain-derived neurotrophic factor, fibroblast growth factor 2 and myristoylated alanine-rich C kinase substrate (Muller et al., 2000; Kanato et al., 2008; Mishra et al., 2010; Ono et al., 2012; Theis et al., 2013).
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NeuroanatomyResearch PaperDivergent impact of the polysialyltransferases ST8SiaII and ST8SiaIV on polysialic acid expression in immature neurons and interneurons of the adult cerebral cortex

Abstract

Section snippets

Experimental procedures

Neocortex

Discussion

Acknowledgments

J Biol Chem

Prog Neurobiol

Neuroscience

Neuroscience

J Biol Chem

J Biol Chem

Brain Res Rev

Neuroscience

Brain Res

Brain Res

Neuroscience

J Biol Chem

Neurosci Res

Epilepsy Behav

Neurochem Int

Eur Neuropsychopharmacol

J Chem Neuroanat

Neuroscience

J Biol Chem

Polysialic acid-directed migration and differentiation of neural precursors are essential for mouse brain development

Mol Cell Biol

Depression-like behaviour in neural cell adhesion molecule (NCAM)-deficient mice and its reversal by an NCAM-derived peptide, FGL

Eur J Neurosci

Newly generated neurons in the amygdala and adjoining cortex of adult primates

Proc Natl Acad Sci U S A

Transient expression of doublecortin during adult neurogenesis

J Comp Neurol

Neuroanatomy
Research Paper
Divergent impact of the polysialyltransferases ST8SiaII and ST8SiaIV on polysialic acid expression in immature neurons and interneurons of the adult cerebral cortex