Picomolar amyloid-? peptides enhance spontaneous astrocyte calcium transients.

ABSTRACT: Amyloid-? (A?) peptides are constitutively produced in the brain throughout life via mechanisms that can be regulated by synaptic activity. Although A? has been extensively studied as the pathological plaque-forming protein species in Alzheimer's disease (AD), little is known about the normal physiological function(s) and signaling pathway(s). We previously discovered that physiologically-relevant, low picomolar amounts of A? can enhance synaptic plasticity and hippocampal-dependent cognition in mice. In this study, we demonstrated that astrocytes are cellular candidates for participating in this type of A? signaling. Using calcium imaging of primary astrocyte cultures, we observed that picomolar amounts of A? peptides can enhance spontaneous intracellular calcium transient signaling. After application of 200 pM A?42 peptides, the frequency and amplitude averages of spontaneous cytosolic calcium transients were significantly increased. These effects were dependent on ?7 nicotinic acetylcholine receptors (?7-nAChRs), as the enhancement effects were blocked by a pharmacological ?7-nAChR inhibitor and in astrocytes from an ?7 deficient mouse strain. We additionally examined evoked intercellular calcium wave signaling but did not detect significant picomolar A?-induced alterations in propagation parameters. Overall, these results indicate that at a physiologically-relevant low picomolar concentration, A? peptides can enhance spontaneous astrocyte calcium transient signaling via ?7-nAChRs. Since astrocyte-mediated gliotransmission has been previously found to have neuromodulatory roles, A? peptides may have a normal physiological function in regulating neuron-glia signaling. Dysfunction of this signaling process may underlie glia-based aspects of AD pathogenesis.

SUBMITTER: Lee L 

PROVIDER: S-EPMC4116306 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature