Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Exposure of Cultured Hippocampal Neurons to the Mitochondrial Uncoupler CCCP Induces a Rapid Growth of Dendritic Processes

Version 1 : Received: 2 August 2023 / Approved: 3 August 2023 / Online: 4 August 2023 (12:39:11 CEST)

A peer-reviewed article of this Preprint also exists.

Kushnireva, L.; Korkotian, E.; Segal, M. Exposure of Cultured Hippocampal Neurons to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Induces a Rapid Growth of Dendritic Processes. Int. J. Mol. Sci. 2023, 24, 12940. Kushnireva, L.; Korkotian, E.; Segal, M. Exposure of Cultured Hippocampal Neurons to the Mitochondrial Uncoupler Carbonyl Cyanide Chlorophenylhydrazone Induces a Rapid Growth of Dendritic Processes. Int. J. Mol. Sci. 2023, 24, 12940.

Abstract

A major route for influx of calcium ions into neurons uses the STIM-Orai1 voltage-independent channel. Once cytosolic calcium ([Ca2+]i) elevates, it activates mitochondrial and endoplasmic calcium stores, to affect downstream molecular pathways. In the present study we employed a novel drug, Carbonyl Cyanide Chlorophenylhydrazone (CCCP), a mitochondrial uncoupler, to explore the role of mitochondria in cultured neuronal morphology. CCCP caused a sustained elevation of [Ca2+]i and, quite surprisingly, a massive increase in density of dendritic filopodia and spines in the affected neurons. This morphological change can be prevented in cultures ex-posed to calcium-free medium, to Orai1 antagonist 2APB, or to cells transfected with domi-nant-negative Orai1 plasmid. It is suggested that CCCP activates mitochondria through influx of calcium, to cause a rapid growth of dendritic processes

Keywords

CCCP, Carbonyl Cyanide m Chlorophenyl Hydrazone; calcium; Orai1; STIM1; mitochondria

Subject

Biology and Life Sciences, Neuroscience and Neurology

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