Astrocytes Reduce Store-Operated Ca2+ Entry in Microglia under the Conditions of an Inflammatory Stimulus and Muscarinic Receptor Blockade

Yoo Jin Kim, You Kyoung Shin, Eunhye Seo, Geun Hee Seol

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Inflammation and loss of cholinergic transmission are involved in neurodegenerative diseases, but possible interactions between them within neurons, astrocytes, and microglia have not yet been investigated. We aimed to compare store-operated Ca2+ entry (SOCE) in neurons, astrocytes, and microglia following cholinergic dysfunction in combination with (or without) an inflammatory stimulus and to investigate the effects of linalyl acetate (LA) on this process. We used the SH-SY5Y, U373, and BV2 cell lines related to neurons, astrocytes, and microglia, respectively. Scopolamine or lipopolysaccharide (LPS) was used to antagonize the muscarinic receptors or induce inflammatory responses, respectively. The concentration of intracellular Ca2+ was measured using Fura-2 AM. Treatment with scopolamine and LPS significantly increased SOCE in the neuron-like cells and microglia but not in the scopolamine-pretreated astrocytes. LA significantly reduced SOCE in the scopolamine-pretreated neuron-like cells and microglia exposed to LPS, which was partially inhibited by the Na+-K+ ATPase inhibitor ouabain and the Na+/Ca2+ exchanger (NCX) inhibitor Ni2+. Notably, SOCE was significantly reduced in the LPS plus scopolamine-pretreated cells mixed with astrocytes and microglia, with a two-fold increase in the applied number of astrocytes. LA may be useful in protecting neurons and microglia by reducing elevated SOCE that is induced by inflammatory responses and inhibiting the muscarinic receptors via Na+-K+ ATPase and the forward mode of NCX. Astrocytes may protect microglia by reducing increased SOCE under the conditions of inflammation and a muscarinic receptor blockade.

Original languageEnglish
Article number1521
JournalPharmaceuticals
Volume15
Issue number12
DOIs
Publication statusPublished - 2022 Dec

Bibliographical note

Funding Information:
This work was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea (NRF-2021R1A2C2004118) and the Institute of Nursing Research, Korea University Grant. This manuscript is a revision of YJK’s master’s thesis from Korea University.

Publisher Copyright:
© 2022 by the authors.

Keywords

  • astrocytes
  • linalyl acetate
  • lipopolysaccharide
  • microglia
  • scopolamine
  • store-operated Ca entry

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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