title: Glutamine synthetase in astrocytes from entorhinal cortex of the triple transgenic animal model of Alzheimer's disease is not affected by pathological progression.
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.
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Manchester, UK.
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Yeh
authors.forename: Alexei
authors.initials: A
authors.lastname: Verkhratsky
authors.forename: Slavica
authors.initials: S
authors.lastname: Terzieva
authors.forename: José J
authors.initials: JJ
authors.lastname: Rodríguez
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000201:enzymology* / Q000473:pathology; D001284:Atrophy; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000201:enzymology* / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D009154:Mutation; D053764:Presenilin-1 / Q000235:genetics; D016875:tau Proteins / Q000235:genetics
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein; D053764:Presenilin-1; D016875:tau Proteins; D005974:Glutamate-Ammonia Ligase