TY - JOUR
T1 - Neurotransmitters and apoptosis in the developing brain
AU - Ikonomidou, Chrysanthy
AU - Bittigau, Petra
AU - Koch, Christian
AU - Genz, Kerstin
AU - Hoerster, Friederike
AU - Felderhoff-Mueser, Ursula
AU - Tenkova, Tatyana
AU - Dikranian, Krikor
AU - Olney, John W.
N1 - Funding Information:
This work was supported by DFG Grant Ik2/2-1 and NIH Grants AG 11355, DA 05072, EY 08089, and HD 37100. J.W.O. is an NARSAD 2000 Toulmin Distinguished Investigator Awardee.
PY - 2001/8/15
Y1 - 2001/8/15
N2 - In the immature mammalian brain during a period of rapid growth (brain growth spurt/synaptogenesis period), neuronal apoptosis can be triggered by the transient blockade of glutamate N-methyl-d-aspartate (NMDA) receptors, or the excessive activation of γ-aminobutyric acid (GABAA) receptors. Apoptogenic agents include anesthetics (ketamine, nitrous oxide, isoflurane, propofol, halothane), anticonvulsants (benzodiazepines, barbiturates), and drugs of abuse (phencyclidine, ketamine, ethanol). In humans, the brain growth spurt period starts in the sixth month of pregnancy and extends to the third year after birth. Ethanol, which has both NMDA antagonist and GABAA agonist properties, is particularly effective in triggering widespread apoptotic neurodegeneration during this vulnerable period. Thus, maternal ingestion of ethanol during the third trimester of pregnancy can readily explain the dysmorphogenic changes in the fetal brain and consequent neurobehavioral disturbances that characterize the human fetal alcohol syndrome. In addition, there is basis for concern that agents used in pediatric and obstetrical medicine for purposes of sedation, anesthesia, and seizure management may cause apoptotic neuronal death in the developing human brain.
AB - In the immature mammalian brain during a period of rapid growth (brain growth spurt/synaptogenesis period), neuronal apoptosis can be triggered by the transient blockade of glutamate N-methyl-d-aspartate (NMDA) receptors, or the excessive activation of γ-aminobutyric acid (GABAA) receptors. Apoptogenic agents include anesthetics (ketamine, nitrous oxide, isoflurane, propofol, halothane), anticonvulsants (benzodiazepines, barbiturates), and drugs of abuse (phencyclidine, ketamine, ethanol). In humans, the brain growth spurt period starts in the sixth month of pregnancy and extends to the third year after birth. Ethanol, which has both NMDA antagonist and GABAA agonist properties, is particularly effective in triggering widespread apoptotic neurodegeneration during this vulnerable period. Thus, maternal ingestion of ethanol during the third trimester of pregnancy can readily explain the dysmorphogenic changes in the fetal brain and consequent neurobehavioral disturbances that characterize the human fetal alcohol syndrome. In addition, there is basis for concern that agents used in pediatric and obstetrical medicine for purposes of sedation, anesthesia, and seizure management may cause apoptotic neuronal death in the developing human brain.
KW - Anesthetics
KW - Apoptosis
KW - Barbiturates
KW - Benzodiazepines
KW - Ethanol
KW - GABA receptors
KW - Ketamine
KW - NMDA receptors
KW - Phencyclidine
KW - Synaptogenesis
KW - Trauma
UR - http://www.scopus.com/inward/record.url?scp=0035882765&partnerID=8YFLogxK
U2 - 10.1016/S0006-2952(01)00696-7
DO - 10.1016/S0006-2952(01)00696-7
M3 - Article
C2 - 11448448
AN - SCOPUS:0035882765
SN - 0006-2952
VL - 62
SP - 401
EP - 405
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 4
ER -