PMID- 18196452
OWN - NLM
STAT- MEDLINE
DCOM- 20080811
LR  - 20181113
IS  - 0272-4340 (Print)
IS  - 1573-6830 (Electronic)
IS  - 0272-4340 (Linking)
VI  - 28
IP  - 3
DP  - 2008 May
TI  - Effects of disrupting calcium homeostasis on neuronal maturation: early 
      inhibition and later recovery.
PG  - 389-409
LID - 10.1007/s10571-007-9255-9 [doi]
AB  - 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.
FAU - Ringler, Sarah L
AU  - Ringler SL
AD  - Neurobiology & Anatomy, Wake Forest University Medical School, Medical Center 
      Boulevard, Winston Salem, NC 27157-1010, USA.
FAU - Aye, Jamie
AU  - Aye J
FAU - Byrne, Erica
AU  - Byrne E
FAU - Anderson, Megan
AU  - Anderson M
FAU - Turner, Christopher P
AU  - Turner CP
LA  - eng
GR  - R01 NS051632/NS/NINDS NIH HHS/United States
GR  - R01 NS051632-02/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080115
PL  - United States
TA  - Cell Mol Neurobiol
JT  - Cellular and molecular neurobiology
JID - 8200709
RN  - 0 (Chelating Agents)
RN  - 526U7A2651 (Egtazic Acid)
RN  - 67526-95-8 (Thapsigargin)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - K22DDW77C0 (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/*antagonists & inhibitors/metabolism/*pharmacology
MH  - Cell Differentiation/*drug effects
MH  - Cells, Cultured
MH  - Chelating Agents/pharmacology
MH  - Dizocilpine Maleate/pharmacology
MH  - Egtazic Acid/analogs & derivatives/pharmacology
MH  - Embryo, Mammalian
MH  - Embryonic Development/drug effects
MH  - Growth Cones/drug effects
MH  - Homeostasis/drug effects
MH  - Models, Biological
MH  - Neurites/drug effects/physiology
MH  - Neurons/*drug effects/metabolism/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Thapsigargin/pharmacology
PMC - PMC2714481
MID - NIHMS124283
EDAT- 2008/01/16 09:00
MHDA- 2008/08/12 09:00
PMCR- 2009/07/23
CRDT- 2008/01/16 09:00
PHST- 2007/09/23 00:00 [received]
PHST- 2007/12/14 00:00 [accepted]
PHST- 2008/01/16 09:00 [pubmed]
PHST- 2008/08/12 09:00 [medline]
PHST- 2008/01/16 09:00 [entrez]
PHST- 2009/07/23 00:00 [pmc-release]
AID - 10.1007/s10571-007-9255-9 [doi]
PST - ppublish
SO  - Cell Mol Neurobiol. 2008 May;28(3):389-409. doi: 10.1007/s10571-007-9255-9. Epub 
      2008 Jan 15.