Neurotransmitters and apoptosis in the developing brain

Chrysanthy Ikonomidou, Petra Bittigau, Christian Koch, Kerstin Genz, Friederike Hoerster, Ursula Felderhoff-Mueser, Tatyana Tenkova, Krikor Dikranian, John W. Olney

Research output: Contribution to journalArticlepeer-review

220 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)401-405
Number of pages5
JournalBiochemical Pharmacology
Volume62
Issue number4
DOIs
StatePublished - Aug 15 2001

Keywords

  • Anesthetics
  • Apoptosis
  • Barbiturates
  • Benzodiazepines
  • Ethanol
  • GABA receptors
  • Ketamine
  • NMDA receptors
  • Phencyclidine
  • Synaptogenesis
  • Trauma

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