Τετάρτη 9 Δεκεμβρίου 2020

Keratan sulfate proteoglycan as an axonal insulating barrier in the forebrain of fetuses with alobar/semi-lobar holoprosencephaly.

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Keratan sulfate proteoglycan as an axonal insulating barrier in the forebrain of fetuses with alobar/semi-lobar holoprosencephaly.

Clin Neuropathol. 2020 Dec 08;:

Authors: Sarnat HB, Yu W, Flores-Sarnat L

Abstract
BACKGROUND: Keratan sulfate (KS) is an abundant proteoglycan in the developing human CNS where it functions as an extracellular axonal guidance molecule, repelling glutamatergic while facilitating -GABAergic axons. It ensheaths axonal fascicles. In fetal brain maturation, KS acts as a barrier to axonal penetration. Its possible role in the pathogenesis of fetal holoprosencephaly (HPE) was studied.
MATERIALS AND METHODS: Forebrains of 6 human fetuses with HPE identified by prenatal ultrasound were examined at autopsy with KS immunoreactivity and other markers of cellular maturation and synaptogenesis, with age-matched controls.
RESULTS: KS was strongly expressed in astrocytes in the thalamus from 13 weeks gestational age (GA) and in globus pallidus but not corpus striatum. Cortical plate reactivity was limited to the molecular zone, where KS was excessive, ensheathing individual transverse molecular zone axons. Axonal envelopment preceding myelination also was seen in the internal capsule and thalamocortical projections, but perifascicular KS was diminished. KS was not expressed in hippocampus in either HPE or controls. Glutamate receptor-2 (GluR2) was evident in hippocampal granular and pyramidal neurons at mid-gestation. KS distribution did not, however, correlate with synaptophysin.
CONCLUSION: Excessive ensheathment of axons by KS provides additional protection of GABAergic inhibitory axons and synapses that may help suppress epileptogenesis. Though involved in selection of excitatory and inhibitory synaptogenesis, KS does not follow a developmental sequence corresponding to synaptophysin or GluR2 reactivities in either HPE or in normal fetal brain.

PMID: 33287953 [PubMed - as supplied by publisher]

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