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Glutamine synthetase in astrocytes from entorhinal cortex of the triple transgenic animal model of Alzheimer’s disease is not affected by pathological progression

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Abstract

Astrocytes are fundamental for brain physiology and pathology, including Alzheimer’s disease (AD). Among their functions, the maintenance of glutamate balance via the glutamate–glutamine (Glu–Gln) shuttle is critical for both normal cognitive functions and excitotoxicity relevant for AD progression. Astroglial glutamine synthetase (GS), converting glutamate to glutamine, is a key element in the Glu–Gln cycle. The entorhinal cortex (EC) is the brain area earliest affected in human AD. We have recently reported an early astrocytic atrophy in the EC in triple transgenic animal model of AD (3×Tg-AD). Here, we studied and analysed whether the changes in astrocytic morphology coincides with alterations of the Glu–Gln cycle by determining astrocytic GS. We found that the numerical density of GS-immunoreactive (GS-IR) cells as well as GS content (measured by optical density, OD) remained constant between 1 and 12 months of age, independent of the presence of senile plaques. Dual labelling images revealed GS-IR, GFAP-IR, GS/GFAP-IR subsets of astroglia. Despite the evident decrease in GFAP-IR surface and volume, the surface and volume of GS-IR and GS/GFAP-IR cells remained unchanged. Therefore, reduced GFAP presence obvious in the progression of AD from early stages does not impair upon glutamate homeostasis in the EC of 3×Tg-AD mice. Our data also indicate distinct functional populations of astrocytes, which may undergo specific remodelling during AD progression.

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Acknowledgments

This study was supported by an Alzheimer’s Research Trust Programme Grant [ART/PG2004A/1] to JJR and AV, grants from the Grant Agency of the Czech Republic to JJR ([GACR 309/09/1696], to ES and JJR [GACR 304/11/0184] and to AV [GACR 305/08/1381, GACR 305/08/1384]) and by the Welcome Trust.. Support from the Spanish Government, Plan Nacional de I+D+I 2008-2011 and ISCIII- Subdirección General de Evaluación y Fomento de la Investigación [PI10/02738] co-financed by FEDER to JJR and AV and the Government of the Basque Country [AE-2010-1-28, AEGV10/16, GV-2011111020] are gratefully acknowledged.

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Authors and Affiliations

  1. Faculty of Life Sciences, The University of Manchester, Manchester, UK

    Chia-Yu Yeh & Alexei Verkhratsky

  2. IKERBASQUE Basque Foundation for Science, 48011, Bilbao, Spain

    Alexei Verkhratsky, Slavica Terzieva & José J. Rodríguez

  3. Department of Neurosciences, University of the Basque Country UPV/EHU, 48940, Leioa, Spain

    Alexei Verkhratsky & José J. Rodríguez

  4. CIBERNED, Technological Park, Bldg. 205, Floor 1. Laida Bidea 48170-Zamudio Vizcaya, Bilbao, Spain

    Alexei Verkhratsky & José J. Rodríguez

  5. Laboratory of Neuroendocrinology-Mole Cell Physiology, Institute of Pathophysiology, University of Ljubljana Medical Faculty, Zaloška cesta 4, 1000, Ljubljana, Slovenia

    Slavica Terzieva

  6. Celica, Biomedical Center, Tehnološki Park 24, 1000, Ljubljana, Slovenia

    Slavica Terzieva

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  1. Chia-Yu Yeh
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  2. Alexei Verkhratsky
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  4. José J. Rodríguez
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Correspondence to José J. Rodríguez.

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Yeh, CY., Verkhratsky, A., Terzieva, S. et al. Glutamine synthetase in astrocytes from entorhinal cortex of the triple transgenic animal model of Alzheimer’s disease is not affected by pathological progression. Biogerontology 14, 777–787 (2013). https://doi.org/10.1007/s10522-013-9456-1

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