Related resources
Full-text held externally
Search for item elsewhere
University researcher(s)
Academic department(s)
Amyloid-beta and Alzheimer's disease type pathology differentially affects the calcium signalling toolkit in astrocytes from different brain regions
Grolla, A A; Sim, J A; Lim, D; Rodriguez, J J; Genazzani, A A; Verkhratsky, A
Cell Death Dis. 2013;4:e623.
Access to files
Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:
Full-text held externally
Abstract
The entorhinal-hippocampal circuit is severely affected in Alzheimer's disease (AD). Here, we demonstrate that amyloid-beta (Abeta) differentially affects primary cultured astrocytes derived from the entorhinal cortex (EC) and from the hippocampus from non-transgenic controls and 3xTg-AD transgenic mice. Exposure to 100 nM of Abeta resulted in increased expression of the metabotropic glutamate receptor type 5 (mGluR5) and its downstream InsP3 receptor type 1 (InsP3R1) in hippocampal but not in EC astrocytes. Amplitudes of Ca(2+) responses to an mGluR5 agonist, DHPG, and to ATP, another metabotropic agonist coupled to InsP3Rs, were significantly increased in Abeta-treated hippocampal but not in EC astrocytes. Previously we demonstrated that senile plaque formation in 3xTg-AD mice triggers astrogliosis in hippocampal but not in EC astrocytes. The different sensitivities of the Ca(2+) signalling toolkit of EC versus hippocampal astrocytes to Abeta may account for the lack of astrogliosis in the EC, which in turn can explain the higher vulnerability of this region to AD.
Keyword(s)
Alzheimer Disease/metabolism/pathology; Amyloid beta-Peptides/*pharmacology; Animals; Astrocytes/cytology/*drug effects/metabolism; Calcium Signaling/drug effects; Calcium/*metabolism; Cells, Cultured; Disease Models, Animal; Entorhinal Cortex/cytology/*metabolism; Hippocampus/cytology/*metabolism; Inositol 1,4,5-Trisphosphate Receptors/metabolism; Mice; Mice, Transgenic; Receptor, Metabotropic Glutamate 5; Receptors, Metabotropic Glutamate/agonists/metabolism
Bibliographic metadata
- Related website http://www.ncbi.nlm.nih.gov/pubmed/23661001
- Grolla, A A Sim, J A Lim, D Rodriguez, J J Genazzani, A A Verkhratsky, A England Cell Death Dis. 2013 May 9;4:e623. doi: 10.1038/cddis.2013.145.