Abstract 3
Category: Basic Science
At the end of the session, participants will be able to:
- To appreciate when and where keratan sulfate (KS) appears in the human fetal forebrain and the nature of proteoglycans in general
- To understand how KS forms a chemical template, temporary for migratory neuroblasts and permanent for axonal fascicles
- To know the method of demonstration of proteoglycans in tissue sections and that they are not visualized by electron microscopy or by neuroimaging
COI Disclosure:
None to disclose.
Harvey B. Sarnat [1,2] and Weiming Yu [3]
[1] Departments of Paediatrics, Pathology (Neuropathology) and Clinical Neurosciences, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada
[2] Alberta Children’s Hospital Research Institute (Owerko Centre)
[3] Department of Pathology and Laboratory Medicine, Alberta Children’s Hospital Calgary, Alberta, Canada
Presenter
Dr. Sarnat is Professor of Paediatrics, Pathology (Neuropathology) and Clinical Neurosciences at the University of Calgary. He is board-certified in Paediatrics and in Neurology in the U.S. and in Neurology by the Royal College of Physicians and Surgeons of Canada. Residency training in paediatrics was at the University of Illinois (Chicago) and in child neurology and neuropathology at the University of Virginia (Charlottesville). His academic interests and most research publications over many years are in the fields of neuroembryology, developmental (fetal and neonatal) neuropathology, brain malformations, neonatal neurology and the neuropathology of childhood epilepsy. He serves on the Editorial Boards of 9 journals and has over 200 research publications in peer-reviewed journals; he has authored, co-authored or edited 12 textbooks, and has contributed chapters to 130 specialty books and monographs. He is a member of the Commission on Neuropathology of the International League Against Epilepsy.
Distinguished awards include giving the keynote Gordon Mathieson Lecture at the 50th anniversary meeting of the Canadian Association of Neuropathologists in 2010 and again in 2021, the Bernard Sachs Research Award and Lecture at the 45th annual meeting of the Child Neurology Society in 2016 and having an annual endowed lectureship in his name at the University of Calgary, the Harvey B. Sarnat Developmental Neuroanatomy and Neuropathology Lectureship, since 2013. He is a frequent invited speaker at many medical congresses and institutions within Canada and internationally in the U.S., Europe, Latin America, Japan, and Australia.
Target Audience:
Pathologists, Residents
Other – Write In (Required): basic neuroscientists
CanMEDS:
Medical Expert (the integrating role), Scholar, Professional
Keratan sulfate is a chemical template for neuroblast migratory pathways and axonal fascicles in human fetal forebrain.
Abstract
Objectives. Timing of keratan sulfate (KS) during morphogenesis in normally developing human fetal forebrain structures was studied. KS is a proteoglycan secreted in fetal brain by astrocytes and radial glia into extracellular parenchyma as granulofilamentous deposits. It envelops neurons except dendritic spines, repels glutamatergic and facilitates GABAergic axons. The same genes are expressed in both neuroblast migration and axonal growth.
Methods. Twenty normal human fetal brains from 9-41 weeks gestational age were studied at autopsy. KS was examined by immunoreactivity in formalin-fixed paraffin sections, plus other markers including synaptophysin, S-100β protein, vimentin and nestin.
Results. Radial and tangential neuroblast migratory pathways from subventricular zone to cortical plate were marked by KS deposits as early as 9wk GA, shortly after neuroblast migration initiated. During later gestation this reactivity gradually diminished and disappeared by term. Long axonal fascicles of the internal capsule and short fascicles of intrinsic bundles of globus pallidus and corpus striatum also appeared as early as 9-12wk, as fascicular sleeves before axons even entered. Intense KS occurs in astrocytic cytoplasm and extracellular parenchyma at 9wk in globus pallidus, 15wk thalamus, 18wk corpus striatum, 22wk cortical plate, and hippocampus postnatally. Corpus callosum and anterior commissure do not exhibit KS at any age. Optic chiasm shows peripheral reactivity but not around intrinsic subfasciculi. Cross-immunoreactivity with aggrecan may confuse molecular distinctions.
Conclusion. KS forms a putative chemical template (but not a structural scaffold) for many long and short axonal fascicles before axons enter and for neuroblast migratory pathways at initiation of migration.