Up-regulation of astrocyte metabotropic glutamate receptor 5 by amyloid-β peptide

Astroglial calcium signalling in Alzheimer's disease

“…In another study the effect of β-amyloid on resting Ca 2+ was even more profound; incubation of cultured rat hippocampal astrocytes with 100 nM oligomeric β-amyloid 1-42 for 4 -6 hours elevated increased resting [Ca 2+ ] i from ~50 nM to 100-150 nM [112]. However, longer exposures (48 hours) of cultured astrocytes to β-amyloid in concentrations ranging between 200 nM and 20 mM did not affect basal [Ca 2+ ] i levels [113,114]. The data on acute effects of β-amyloid on astroglial cells in vitro and in slices are controversial.…”

“…The data on acute effects of β-amyloid on astroglial cells in vitro and in slices are controversial. While several laboratories reported that β-amyloid (at 100 nM -5 µM) concentrations triggered transient [Ca 2+ ] i increases or [Ca 2+ ] i oscillations [98,[115][116][117][118][119], others have not found acute [Ca 2+ ] i responses to β-amyloid [112][113][114]. This seemingly incongruent findings could possibly be attributed to variability of β-amyloid species used.…”

“…At longer exposure times (24-72 h), β-amyloid upregulated the expression of astroglial mGluR5 [125]. Incidentally, the up-regulation of mGluR5 has been also found in plaque-surrounding cortical astrocytes associated with senile plaques in the APPswe/PS1dE9 mouse model, as well as in post-mortem human tissues [112,113]. As alluded to earlier, α7 nicotinic cholinoreceptor (α7nAChR) binds β -amyloid with high affinity and can be modulated by ιτ is [126].…”

Calcium Signaling and Amyloid Toxicity in Alzheimer Disease

“…More subtle interactions of A␤ with Ca 2ϩ -regulating G-protein-coupled membrane proteins have also been uncovered. Preincubation with the A␤ 1-40 peptide enhances both the expression of G q -coupled metabotropic glutamate receptor 5, which generates the Ca 2ϩ -mobilizing messenger IP 3 , and the intracellular Ca 2ϩ response to the group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine (78). A␤ also interferes with the interplay between the APP haloprotein and G o , which leads to G-protein-coupled Ca 2ϩ activation and eventually cell death (79).…”

Endoplasmic Reticulum Ca2+Handling in Excitable Cells in Health and Disease

“…A␤ 42 peptides have been shown to increase RyR3 expression in transgenic mouse models of AD (Supnet et al, 2006 as well as to increase the RyR open channel probability, resulting in increased Ca 2ϩ flux (Shtifman et al, 2010). Likewise, A␤ peptides increase the IP 3 -evoked Ca 2ϩ response in neurons directly (Schapansky et al, 2007), as well as indirectly through the alteration of G q -coupled mGlurR5 receptors (Casley et al, 2009;Renner et al, 2010). On the other hand, by impairing coupling of muscarinic acetylcholine receptors to Gq11 via a membrane lipid peroxidation-mediated mechanism, A␤ can suppress Ca 2ϩ responses to acetylcholine (Kelly et al, 1996).…”