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Transgenic overexpression of polysialyltransferase ST8SiaIV under the control of a neuron-specific promoter does not affect brain development but impairs exploratory behavior.

Simon Ngamli Fewou | Iris Röckle | Herbert Hildebrandt | Matthias Eckhardt
Glycobiology | 2019

A large body of the literature has demonstrated that the polysialic acid (polySia) modification of the neural cell adhesion molecule (NCAM) is a key regulator of cellular interactions during brain development, maintenance and plasticity. To properly fulfill these functions, polySia concentration has to be carefully controlled. This is done by the regulation of the expression of the two polySia-synthesizing enzymes ST8SiaII and ST8SiaIV. From this point of view we and others have demonstrated that downregulation of ST8SiaIV during oligodendrocyte differentiation is a prerequisite for efficient myelin formation and maintenance. Here, we addressed the question whether the prevention of polySia downregulation in neurons affects brain and particularly myelin development and functioning. For this purpose, we developed transgenic (tg) mouse lines overexpressing the polysialyltransferase ST8SiaIV in neurons. tg expression of ST8SiaIV prevented the postnatal downregulation of polySia, and most of the polySias in the forebrain and brain stem of adult tg mice were associated with NCAM-140 and NCAM-180 isoforms. Structural examination of the brain revealed no overt abnormalities of axons and myelin. In addition, ultrastructural and western blot analyses indicated normal myelin development. However, behavioral studies revealed reduced rearing activity, a measure for exploratory behavior, while parameters of motor activity were not affected in tg mice. Taken together, these results suggest that a persisting presence of polySia in neurons has no major effect on brain structure, myelination and myelin maintenance, but causes mild behavioral changes.

Pubmed ID: 31147692

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Molecular Probes (tool)

RRID:SCR_013318

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

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RRID:IMSR_JAX:000664

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RRID:SCR_014296

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RRID:SCR_003070

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RRID:SCR_002677

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RRID:SCR_002677

Digital image processing system where microscope settings and processing steps may be adjusted in single user interface. Can acquire images from variety of cameras. Includes software package for capturing, archiving and preparing images for publication. Allows users to visualize and present images in several dimensions. Functionality of imaging toolbox expands constantly with wide range of different modules that are tailored to specific applications or microscope accessories. This resource is duplicated by SCR_018376

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AIDA Toolkit (software resource)

RRID:SCR_005914

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GraphPad Prism (software resource)

RRID:SCR_002798

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