Effects of disrupting calcium homeostasis on neuronal maturation: early inhibition and later recovery

Cellular and Molecular Neurobiology
S L RinglerChristopher Paul Turner

Abstract

It has become increasingly clear that agents that disrupt calcium homeostasis may also be toxic to developing neurons. Using isolated primary neurons, we sought to understand the neurotoxicity of agents such as MK801 (which blocks ligand-gated calcium entry), BAPTA (which chelates intracellular calcium), and thapsigargin (TG; which inhibits the endoplasmic reticulum Ca(2+)-ATPase pump). Thus, E18 rat cortical neurons were grown for 1 day in vitro (DIV) and then exposed to vehicle (0.1% DMSO), MK801 (0.01-20 microM), BAPTA (0.1-20 microM), or TG (0.001-1 microM) for 24 h. We found that all three agents could profoundly influence early neuronal maturation (growth cone expansion, neurite length, neurite complexity), with the order of potency being MK801 < BAPTA < TG. We next asked if cultures exposed to these agents were able to re-establish their developmental program once the agent was removed. When we examined network maturity at 4 and 7 DIV, the order of recovery was MK801 > BAPTA > TG. Thus, mechanistically distinct ways of disrupting calcium homeostasis differentially influenced both short-term and long-term neuronal maturation. These observations suggest that agents that act by altering intracellular calcium and are used in...Continue Reading

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Citations

Jul 1, 2009·Experimental Brain Research·Amanda LyallChristopher Paul Turner
Nov 4, 2009·Experimental Brain Research·Christopher Paul TurnerChun Liu
Sep 11, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ana M RomeroJaime Renau-Piqueras
Jul 28, 2012·International Journal of Molecular Sciences·Xi LeiJun Zhang
Mar 13, 2012·Neuroscience·C P TurnerA Phillips
Mar 30, 2011·Pharmacology, Biochemistry, and Behavior·Irma E Holopainen, Hanna B Laurén
Apr 12, 2015·Experimental Neurology·Jin Hwan LeeShan Ping Yu
Apr 14, 2016·Molecular and Cellular Neurosciences·Jennilee M DavidsonDorota A Crawford
Jun 29, 2021·Médecine sciences : M/S·Ekin UcuncuVincent Cantagrel

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