科研之友
微信
新浪微博
Facebook
分享链接
摘要
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-beta (A beta), the toxic trigger for Alzheimer%26apos;s disease (AD), interacts with hippocampal alpha 7 nicotinic acetylcholine receptors (nAChRs). Since alpha 7nAChRs are highly permeable to calcium and are expressed on hippocampal astrocytes, we investigated whether A beta could activate astrocytic alpha 7nAChRs in hippocampal slices and induce GT glutamate release. We found that biologically-relevant concentrations of A beta(1-42) elicited alpha 7nAChR-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 A beta 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 A beta observed in this model. Activation of alpha 7nAChRs on WT astrocytes increased spontaneous inward currents on pyramidal neurons while alpha 7nAChRs 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.
- 出版日期2013-11-28
