WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience Join the Society for Neuroscience
QUICK SEARCH:   [advanced]


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
This Article
Right arrow Full Text (PDF)
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Didier, M.
Right arrow Articles by Berman, S. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Didier, M.
Right arrow Articles by Berman, S. A.

 Previous Article  |  Next Article 

Journal of Neuroscience, Vol 16, 2238-2250, Copyright © 1996 by Society for Neuroscience

ARTICLE

DNA strand breaks induced by sustained glutamate excitotoxicity in primary neuronal cultures

M Didier, S Bursztajn, E Adamec, L Passani, RA Nixon, JT Coyle, JY Wei and SA Berman
Laboratories for Molecular Neuroscience, McLean Hospital, Belmont, Massachusetts 02178, USA.

We developed a new approach to study single- and double-stranded DNA breaks during chronic, moderate excitotoxicity resulting from the inhibition of the glutamate transporter in cerebellar granule cell primary cultures. A 24 hr treatment of 2-week-old cultures with L-alpha- amino adipate (LAA), an inhibitor of the cerebellar glutamate uptake transporter, caused a gradual extracellular accumulation of endogenous glutamate that induced reversible morphological change of granule neurons but no neuronal cell death despite sustained, but moderate, elevations of the free intracellular calcium concentrations. Nick translation experiments on isolated nuclei or cells from cerebellar cultures chronically exposed to LAA revealed increased radioactive nucleotide incorporation indicative of DNA nicking. This LAA effect was dose-dependent and suppressed by NMDA receptor antagonists. Cultures treated for 24 hr with LAA and subjected to in situ nick translation showed an intense nuclear labeling of neurons but not glia, which could be abolished by MK801. A similar labeling was also observed in altered nuclei of granule neurons acutely exposed to high glutamate concentrations or undergoing an apoptotic cell death. Although the TUNEL labeling method detected no DNA double-strand breaks in LAA- treated cerebellar cultures, it displayed clear evidence of DNA damage during acute glutamate excitotoxicity or during apoptosis. However, Southern blot analysis of nuclear DNA revealed a DNA laddering only in apoptotic cell death. Our results demonstrate that DNA damage, characterized by DNA single-strand breaks, is an early event in chronic, moderate excitotoxicity. This type of DNA degradation, which appears before any nuclear morphological changes, is distinct from the massive DNA single- and/or double-strand damages observed during acute glutamate excitotoxicity or apoptosis.


This article has been cited by other articles:


Home page
 Toxicol SciHome page
A. Rogers, G. Schmuck, G. Scholz, and D. C. Williams
c-fos mRNA Expression in Rat Cortical Neurons During Glutamate-Mediated Excitotoxicity
Toxicol. Sci., December 1, 2004; 82(2): 562 - 569.
[Abstract] [Full Text] [PDF]

Home page
 NeuroscientistHome page
W. B. Jacobs, G. S. Walsh, and F. D. Miller
Neuronal Survival and p73/p63/p53: A Family Affair
Neuroscientist, October 1, 2004; 10(5): 443 - 455.
[Abstract] [PDF]

Home page
 Arch Gen PsychiatryHome page
F. M. Benes, J. Walsh, S. Bhattacharyya, A. Sheth, and S. Berretta
DNA Fragmentation Decreased in Schizophrenia but Not Bipolar Disorder
Arch Gen Psychiatry, April 1, 2003; 60(4): 359 - 364.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
W. Fu, C. Lu, and M. P. Mattson
Telomerase Mediates the Cell Survival-Promoting Actions of Brain-Derived Neurotrophic Factor and Secreted Amyloid Precursor Protein in Developing Hippocampal Neurons
J. Neurosci., December 15, 2002; 22(24): 10710 - 10719.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
L. Virag and C. Szabo
The Therapeutic Potential of Poly(ADP-Ribose) Polymerase Inhibitors
Pharmacol. Rev., September 1, 2002; 54(3): 375 - 429.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. Mirjany, L. Ho, and G. M. Pasinetti
Role of Cyclooxygenase-2 in Neuronal Cell Cycle Activity and Glutamate-Mediated Excitotoxicity
J. Pharmacol. Exp. Ther., May 1, 2002; 301(2): 494 - 500.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
E. T. Donnelly, M. O'Connell, N. McClure, and S. E.M. Lewis
Differences in nuclear DNA fragmentation and mitochondrial integrity of semen and prepared human spermatozoa
Hum. Reprod., July 1, 2000; 15(7): 1552 - 1561.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Lankiewicz, C. Marc Luetjens, N. Truc Bui, A. J. Krohn, M. Poppe, G. M. Cole, T. C. Saido, and J. H. M. Prehn
Activation of Calpain I Converts Excitotoxic Neuron Death into a Caspase-independent Cell Death
J. Biol. Chem., May 26, 2000; 275(22): 17064 - 17071.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. J. Chong, M. R. Murray, E. C. Gosink, H. R. C. Russell, A. Srinivasan, M. Kapsetaki, S. J. Korsmeyer, and P. J. McKinnon
Atm and Bax cooperate in ionizing radiation-induced apoptosis in the central nervous system
PNAS, January 18, 2000; 97(2): 889 - 894.
[Abstract] [Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
A. M. Vincent and K. Maiese
Direct Temporal Analysis of Apoptosis Induction in Living Adherent Neurons
J. Histochem. Cytochem., May 1, 1999; 47(5): 661 - 672.
[Abstract] [Full Text]

Home page
 J. Neurosci.Home page
T. Nagayama, A. D. Sinor, R. P. Simon, J. Chen, S. H. Graham, K. Jin, and D. A. Greenberg
Cannabinoids and Neuroprotection in Global and Focal Cerebral Ischemia and in Neuronal Cultures
J. Neurosci., April 15, 1999; 19(8): 2987 - 2995.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
S. Bursztajn, R. DeSouza, D. L. McPhie, S. A. Berman, J. Shioi, N. K. Robakis, and R. L. Neve
Overexpression in Neurons of Human Presenilin-1 or a Presenilin-1 Familial Alzheimer Disease Mutant Does Not Enhance Apoptosis
J. Neurosci., December 1, 1998; 18(23): 9790 - 9799.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
R. Sankar, D. H. Shin, H. Liu, A. Mazarati, A. Pereira de Vasconcelos, and C. G. Wasterlain
Patterns of Status Epilepticus-Induced Neuronal Injury during Development and Long-Term Consequences
J. Neurosci., October 15, 1998; 18(20): 8382 - 8393.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
H. Xiang, Y. Kinoshita, C. M. Knudson, S. J. Korsmeyer, P. A. Schwartzkroin, and R. S. Morrison
Bax Involvement in p53-Mediated Neuronal Cell Death
J. Neurosci., February 15, 1998; 18(4): 1363 - 1373.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
Z. Pang and J. W. Geddes
Mechanisms of Cell Death Induced by the Mitochondrial Toxin 3-Nitropropionic Acid: Acute Excitotoxic Necrosis and Delayed Apoptosis
J. Neurosci., May 1, 1997; 17(9): 3064 - 3073.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
H. Xiang, D. W. Hochman, H. Saya, T. Fujiwara, P. A. Schwartzkroin, and R. S. Morrison
Evidence for p53-Mediated Modulation of Neuronal Viability
J. Neurosci., November 1, 1996; 16(21): 6753 - 6765.
[Abstract] [Full Text] [PDF]


-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2008 by Society for Neuroscience ONLINE ISSN: 1529-2401
-