Beta Amyloid Peptide: Research Paper : The Anemonia sulcata Toxin BDS-I Protects Astrocytes Exposed to Aβ 1-42 Oligomers by Restoring [Ca 2+] i Transients and ER Ca 2+ Signaling

The Anemonia sulcata Toxin BDS-I Protects Astrocytes Exposed to Aβ 1-42 Oligomers by Restoring [Ca 2+] i Transients and ER Ca 2+ Signaling

Abstract

Intracellular calcium concentration ([Ca2+]i) transients in astrocytes represent a highly plastic signaling pathway underlying the communication between neurons and glial cells. However, how this important phenomenon may be compromised in Alzheimer's disease (AD) remains unexplored. Moreover, the involvement of several K+ channels, including KV3.4 underlying the fast-inactivating currents, has been demonstrated in several AD models. Here, the effect of KV3.4 modulation by the marine toxin blood depressing substance-I (BDS-I) extracted from Anemonia sulcata has been studied on [Ca2+]i transients in rat primary cortical astrocytes exposed to Aβ1-42 oligomers. We showed that: (1) primary cortical astrocytes expressing KV3.4 channels displayed [Ca2+]i transients depending on the occurrence of membrane potential spikes, (2) BDS-I restored, in a dose-dependent way, [Ca2+]i transients in astrocytes exposed to Aβ1-42 oligomers (5 µM/48 h) by inhibiting hyperfunctional KV3.4 channels, (3) BDS-I counteracted Ca2+ overload into the endoplasmic reticulum (ER) induced by Aβ1-42 oligomers, (4) BDS-I prevented the expression of the ER stress markers including active caspase 12 and GRP78/BiP in astrocytes treated with Aβ1-42 oligomers, and (5) BDS-I prevented Aβ1-42-induced reactive oxygen species (ROS) production and cell suffering measured as mitochondrial activity and lactate dehydrogenase (LDH) release. Collectively, we proposed that the marine toxin BDS-I, by inhibiting the hyperfunctional KV3.4 channels and restoring [Ca2+]i oscillation frequency, prevented Aβ1-42-induced ER stress and cell suffering in astrocytes.

Keywords: Aβ1–42 oligomers; BDS-I; ER stress; KV3.4 channel; [Ca2+]i transients; astrocytes.

This article originally appeared in the "https://pubmed.ncbi.nlm.nih.gov/33396295/" and has their copyrights. We do not claim copyright on the content. This information is for research purposes only. This Blog is made available by publishers for educational purposes only as well as to give you general information and a general understanding , not to provide specific advice. By using this blog site you understand that there is no client relationship between you and the Blog publisher. The Blog should not be used as a substitute for competent research advice.