α7 nicotinic receptor-mediated astrocytic gliotransmitter release: Aβ effects in a preclinical Alzheimer's mouse model

Tiina Maria Pirttimaki, Neela Krushna Codadu, Alia Awni, Pandey Pratik, David Andrew Nagel, Eric James Hill, Kelly Tennyson Dineley, H. Rheinallt Parri

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Abstract

It is now recognized that astrocytes participate in synaptic communication through intimate interactions with neurons. A principal mechanism is through the release of gliotransmitters (GTs) such as ATP, D-serine and most notably, glutamate, in response to astrocytic calcium elevations. We and others have shown that amyloid-β (Aβ), the toxic trigger for Alzheimer's disease (AD), interacts with hippocampal α7 nicotinic acetylcholine receptors (nAChRs). Since α7nAChRs are highly permeable to calcium and are expressed on hippocampal astrocytes, we investigated whether Aβ could activate astrocytic α7nAChRs in hippocampal slices and induce GT glutamate release. We found that biologically-relevant concentrations of Aβ1-42 elicited α7nAChR-dependent calcium elevations in hippocampal CA1 astrocytes and induced NMDAR-mediated slow inward currents (SICs) in CA1 neurons. In the Tg2576 AD mouse model for Aβ over-production and accumulation, we found that spontaneous astrocytic calcium elevations were of higher frequency compared to wildtype (WT). The frequency and kinetic parameters of AD mice SICs indicated enhanced gliotransmission, possibly due to increased endogenous Aβ observed in this model. Activation of α7nAChRs on WT astrocytes increased spontaneous inward currents on pyramidal neurons while α7nAChRs on astrocytes of AD mice were abrogated. These findings suggest that, at an age that far precedes the emergence of cognitive deficits and plaque deposition, this mouse model for AD-like amyloidosis exhibits augmented astrocytic activity and glutamate GT release suggesting possible repercussions for preclinical AD hippocampal neural networks that contribute to subsequent cognitive decline.

Original languageEnglish (US)
Article numbere81828
JournalPloS one
Volume8
Issue number11
DOIs
StatePublished - Nov 28 2013

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Pirttimaki, T. M., Codadu, N. K., Awni, A., Pratik, P., Nagel, D. A., Hill, E. J., Dineley, K. T., & Parri, H. R. (2013). α7 nicotinic receptor-mediated astrocytic gliotransmitter release: Aβ effects in a preclinical Alzheimer's mouse model. PloS one, 8(11), [e81828]. https://doi.org/10.1371/journal.pone.0081828