bernard
04-11-2004, 12:16 PM
http://www.sciencedirect.com/science/journal/00068993
Volume 1028 issue 1 (impossible to give a good link, the written link does not work).
Research report
In the adult CNS, ethanol prevents rather than produces NMDA antagonist-induced neurotoxicity
Nuri B. Farber, , Corey Heinkel, William H. Dribben, Brian Nemmers and Xiaoping Jiang
Department of Psychiatry, Washington University, Campus Box 8134 660 S. Euclid Ave. St. Louis, MO, 63110-1093, United States
Accepted 29 August 2004. Available online 5 October 2004.
Abstract
Single doses of an NMDA antagonist cause an adult or a prepubertal form of neurodegeneration, depending on the age of the animal. Single doses of ethanol (EtOH) by blocking NMDA receptors produce apoptotic neurodegeneration in young animals. This capability could account, in part, for the ability of EtOH to produce the fetal alcohol syndrome. We investigated whether EtOH could produce NMDA antagonist-induced neurotoxicity (NAN), a different neurotoxicity that is seen only in adult animals. In spite of producing blood EtOH levels (30 to 600 mg/dl) known to block NMDA receptors, EtOH was unable to produce neurotoxicity in the adult central nervous system (CNS). Moreover, EtOH in a dose-dependent fashion (ED50=138 mg/dl) prevented the selective and powerful NMDA antagonist, MK-801, from producing NAN in adult animals, suggesting that activity at another site might be negating the neurotoxic effect of EtOH's inherent NMDA antagonistic activity. Because GABAA agonism and non-NMDA glutamate antagonism, properties which EtOH possesses, can prevent NAN, we proceeded to study whether GABAA antagonists (or agents capable of reversing EtOH's GABAergic effects) and non-NMDA agonists could reverse EtOH's protective effect. Bicuculline, Ro15-4513, finasteride, kainic acid or AMPA, alone or in combination, did not significantly reverse EtOH's protective effect. Given that EtOH has effects on a wide range of ion channels and receptors, determining the precise mechanism of EtOH's protective effect will take additional effort. The inability of EtOH to acutely produce NAN in the adult CNS indicates that, in contrast to fetuses, brief exposure of the adult CNS to EtOH is non-toxic for neurons.
Keywords: Ethanol; Neurodegeneration; Neurotoxicity; NMDA glutamate antagonist; GABAA receptor; Non-NMDA Glu receptor; Psychosis
Neuroscience classification codes: Disorders of the nervous system, Neurotoxicity
Corresponding author. Tel.: +1 314 362 2459; fax: +1 314 362 9902.
I understand now, why French people have good neurons!?
Volume 1028 issue 1 (impossible to give a good link, the written link does not work).
Research report
In the adult CNS, ethanol prevents rather than produces NMDA antagonist-induced neurotoxicity
Nuri B. Farber, , Corey Heinkel, William H. Dribben, Brian Nemmers and Xiaoping Jiang
Department of Psychiatry, Washington University, Campus Box 8134 660 S. Euclid Ave. St. Louis, MO, 63110-1093, United States
Accepted 29 August 2004. Available online 5 October 2004.
Abstract
Single doses of an NMDA antagonist cause an adult or a prepubertal form of neurodegeneration, depending on the age of the animal. Single doses of ethanol (EtOH) by blocking NMDA receptors produce apoptotic neurodegeneration in young animals. This capability could account, in part, for the ability of EtOH to produce the fetal alcohol syndrome. We investigated whether EtOH could produce NMDA antagonist-induced neurotoxicity (NAN), a different neurotoxicity that is seen only in adult animals. In spite of producing blood EtOH levels (30 to 600 mg/dl) known to block NMDA receptors, EtOH was unable to produce neurotoxicity in the adult central nervous system (CNS). Moreover, EtOH in a dose-dependent fashion (ED50=138 mg/dl) prevented the selective and powerful NMDA antagonist, MK-801, from producing NAN in adult animals, suggesting that activity at another site might be negating the neurotoxic effect of EtOH's inherent NMDA antagonistic activity. Because GABAA agonism and non-NMDA glutamate antagonism, properties which EtOH possesses, can prevent NAN, we proceeded to study whether GABAA antagonists (or agents capable of reversing EtOH's GABAergic effects) and non-NMDA agonists could reverse EtOH's protective effect. Bicuculline, Ro15-4513, finasteride, kainic acid or AMPA, alone or in combination, did not significantly reverse EtOH's protective effect. Given that EtOH has effects on a wide range of ion channels and receptors, determining the precise mechanism of EtOH's protective effect will take additional effort. The inability of EtOH to acutely produce NAN in the adult CNS indicates that, in contrast to fetuses, brief exposure of the adult CNS to EtOH is non-toxic for neurons.
Keywords: Ethanol; Neurodegeneration; Neurotoxicity; NMDA glutamate antagonist; GABAA receptor; Non-NMDA Glu receptor; Psychosis
Neuroscience classification codes: Disorders of the nervous system, Neurotoxicity
Corresponding author. Tel.: +1 314 362 2459; fax: +1 314 362 9902.
I understand now, why French people have good neurons!?