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

Autor: Ringler SL; Neurobiology & Anatomy, Wake Forest University Medical School, Medical Center Boulevard, Winston Salem, NC 27157-1010, USA., Aye J, Byrne E, Anderson M, Turner CP
Jazyk: angličtina
Zdroj: Cellular and molecular neurobiology [Cell Mol Neurobiol] 2008 May; Vol. 28 (3), pp. 389-409. Date of Electronic Publication: 2008 Jan 15.
DOI: 10.1007/s10571-007-9255-9
Abstrakt: 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 obstetrics or neonatology may be quite harmful to the still-developing human brain.
Databáze: MEDLINE
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