Astrocytic glutamine synthetase is expressed in the neuronal somatic layers and down-regulated proportionally to neuronal loss in the human epileptic hippocampus

• Verfasst von: Papageorgiou, Ismini E. [VerfasserIn]
• Verfasst von: Valous, Nektarios A. [VerfasserIn]
• Verfasst von: Lahrmann, Bernd [VerfasserIn]
• Verfasst von: Grabe, Niels [VerfasserIn]
• Verfasst von: Halama, Niels [VerfasserIn]
• Verfasst von: Kann, Oliver [VerfasserIn]
• Titel: Astrocytic glutamine synthetase is expressed in the neuronal somatic layers and down-regulated proportionally to neuronal loss in the human epileptic hippocampus
• Verf.angabe: Ismini E. Papageorgiou, Nektarios A. Valous, Bernd Lahrmann, Hana Janova, Zin-Juan Klaft, Arend Koch, Ulf C. Schneider, Peter Vajkoczy, Frank L. Heppner, Niels Grabe, Niels Halama, Uwe Heinemann, Oliver Kann
• E-Jahr: 2018
• Jahr: 19 January 2018
• Umfang: 14 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 24.02.2020
• Titel Quelle: Enthalten in: Glia
• Ort Quelle: Bognor Regis [u.a.] : Wiley-Liss, 1988
• Jahr Quelle: 2018
• Band/Heft Quelle: 66(2018), 5, Seite 920-933
• ISSN Quelle: 1098-1136
• DOI: doi:10.1002/glia.23292
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: astroglia
• Sach-SW: digital pathology
• Sach-SW: GFAP
• Sach-SW: hippocampal sclerosis
• Sach-SW: stereology
• K10plus-PPN: 1690879009

Abstract

Human mesial temporal lobe epilepsy (MTLE) features subregion-specific hippocampal neurodegeneration and reactive astrogliosis, including up-regulation of the glial fibrillary acidic protein (GFAP) and down-regulation of glutamine synthetase (GS). However, the regional astrocytic expression pattern of GFAP and GS upon MTLE-associated neurodegeneration still remains elusive. We assessed GFAP and GS expression in strict correlation with the local neuronal number in cortical and hippocampal surgical specimens from 16 MTLE patients using immunohistochemistry, stereology and high-resolution image analysis for digital pathology and whole-slide imaging. In the cortex, GS-positive (GS+) astrocytes are dominant in all neuronal layers, with a neuron to GS+ cell ratio of 2:1. GFAP-positive (GFAP+) cells are widely spaced, with a GS+ to GFAP+ cell ratio of 3:1-5:1. White matter astrocytes, on the contrary, express mainly GFAP and, to a lesser extent, GS. In the hippocampus, the neuron to GS+ cell ratio is approximately 1:1. Hippocampal degeneration is associated with a reduction of GS+ astrocytes, which is proportional to the degree of neuronal loss and primarily present in the hilus. Up-regulation of GFAP as a classical hallmark of reactive astrogliosis does not follow the GS-pattern and is prominent in the CA1. Reactive alterations were proportional to the neuronal loss in the neuronal somatic layers (stratum pyramidale and hilus), while observed to a lesser extent in the axonal/dendritic layers (stratum radiatum, molecular layer). We conclude that astrocytic GS is expressed in the neuronal somatic layers and, upon neurodegeneration, is down-regulated proportionally to the degree of neuronal loss.