Astrocytes respond to a neurotoxic Aβ fragment with state-dependent Ca 2+ alteration and multiphasic transmitter release - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Acta Neuropathologica Communications Year : 2021

Astrocytes respond to a neurotoxic Aβ fragment with state-dependent Ca 2+ alteration and multiphasic transmitter release

Viet Cuong Pham
Karine Hérault
  • Function : Author
Martin Oheim
Bruno Cauli

Abstract

Excessive amounts of amyloid β (Aβ) peptide have been suggested to dysregulate synaptic transmission in Alzheimer's disease (AD). As a major type of glial cell in the mammalian brain, astrocytes regulate neuronal function and undergo activity alterations upon Aβ exposure. Yet the mechanistic steps underlying astrocytic responses to Aβ peptide remain to be elucidated. Here by fluorescence imaging of signaling pathways, we dissected astrocytic responses to Aβ25-35 peptide, a neurotoxic Aβ fragment present in AD patients. In native health astrocytes, Aβ25-35 evoked Ca 2+ elevations via purinergic receptors, being also dependent on the opening of connexin (CX) hemichannels. Aβ25-35, however, induced a Ca 2+ diminution in Aβ-preconditioned astrocytes as a result of the potentiation of the plasma membrane Ca 2+ ATPase (PMCA). The PMCA and CX protein expression was observed with immunostaining in the brain tissue of hAPPJ20 AD mouse model. We also observed both Ca 2+-independent and Ca 2+-dependent glutamate release upon astrocytic Aβ exposure, with the former mediated by CX hemichannel and the latter by both anion channels and lysosome exocytosis. Our results suggest that Aβ peptide causes state-dependent responses in astrocytes, in association with a multiphasic release of signaling molecules. This study therefore helps to understand astrocyte engagement in AD-related amyloidopathy.
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hal-03182439 , version 1 (26-03-2021)

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Viet Cuong Pham, Karine Hérault, Martin Oheim, Steeve Maldera, Vincent Vialou, et al.. Astrocytes respond to a neurotoxic Aβ fragment with state-dependent Ca 2+ alteration and multiphasic transmitter release. Acta Neuropathologica Communications, 2021, 9 (1), pp.44. ⟨10.1186/s40478-021-01146-1⟩. ⟨hal-03182439⟩
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