Author/Editor     Yeh, Chia-Yu; Verkhratsky, Alexei; Terzieva, Slavica; Rodríguez, José J.
Title     Glutamine synthetase in astrocytes from entorhinal cortex of the triple transgenic animal model of Alzheimer's disease is not affected by pathological progression
Type     članek
Vol. and No.     Letnik 14, št. 6
Publication year     2013
Volume     str. 777-787
ISSN     1573-6768 - Biogerontology
Language     eng
Abstract     Astrocytes are fundamental for brain physiology and pathology, including Alzheimers disease (AD). Among their functions, the maintenance of glutamate balance via the glutamateglutamine (GluGln) 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 GluGln 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 (3Tg-AD). Here, we studied and analysed whether the changes in astrocytic morphology coincides with alterations of the GluGln 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 3Tg-AD mice. Our data also indicate distinct functional populations of astrocytes, which may undergo specific remodelling during AD progression.
Keywords     Alzheimer's disease
astrocytes
glutamine synthetase
Alzheimerjeva bolezen
astrociti
sintetaza glutamina