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Glia. 2018 May;66(5):920-933. doi: 10.1002/glia.23292. Epub 2018 Jan 19.

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

Author information

1
Institute of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, Heidelberg, D-69120, Germany.
2
Interdisciplinary Center for Neurosciences, University of Heidelberg, Im Neuenheimer Feld 364, Heidelberg, D-69120, Germany.
3
Present address: Institute of Radiology, Südharz Klinikum Nordhausen gGmbH, Dr.-Robert-Koch-Str. 39, Nordhausen, D-99734, Germany.
4
Applied Tumor Immunity Clinical Cooperation Unit, National Center for Tumor Diseases, German Cancer Research Center, Im Neuenheimer Feld 460, Heidelberg, D-69120, Germany.
5
Department of Medical Oncology, National Center for Tumor Diseases, University Hospital Heidelberg, Im Neuenheimer Feld 460, Heidelberg, D-69120, Germany.
6
Hamamatsu Tissue Imaging and Analysis Center (TIGA), National Center for Tumor Diseases, BIOQUANT, Im Neuenheimer Feld 267, University of Heidelberg, Heidelberg, D-69120, Germany.
7
Steinbeis Transfer Center for Medical Systems Biology, Heckerstr. 9, Heidelberg, D-69124, Germany.
8
Division of Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Hermann-Rein-str. 3, Göttingen, D-37075, Germany.
9
Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, Berlin, D-10117, Germany.
10
Neuroscience Research Center, Charité-Universitätsmedizin Berlin, Charitéplatz 1, Berlin, D-10117, Germany.
11
Institute of Neuropathology, Charité-Universitätsmedizin Berlin, Charité Campus Mitte, Charitéplatz 1, Berlin, D-10117, Germany.
12
Department of Neurosurgery, Charité-Universitätsmedizin Berlin, Campus Virchow Medical Center, Augustenplatz 1, Berlin, D-11353, Germany.

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.

KEYWORDS:

GFAP; astroglia; digital pathology; hippocampal sclerosis; stereology

PMID:
29350438
DOI:
10.1002/glia.23292
[Indexed for MEDLINE]

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