Single-dose ketamine administration induces apoptosis in neonatal mouse brain

Michael Rudin, Yeshayahu Katz, Ron Ben-Abraham, Vered Gazit, Yevgeney Tendier, Vadim Tashlykov

Research output: Contribution to journalArticlepeer-review

Abstract

The activity of N-methyl-D-aspartate (NMDA) receptors is critical for neuronal survival in the immature brain. Studies have reported that chronic blockage of these receptors mediates apoptosis in neonatal animals. We investigated the apoptotic effect of a clinically relevant single dose of ketamine, an NMDA receptor antagonist, in the brain of neonatal mice. Seven-day-old ICR mice were injected with ketamine (1.25, 2.5, 5, 10, 20, and 40 mg/kg body weight, subcutaneously in 0.9% NaCl) or with 0.9% NaCl alone as control. Righting reflex testing was performed and mouse brains were examined at 24, 48, and 72 h and 7 days after injection. The number of degenerating neurons was measured using silver staining. Apoptosis was confirmed by DNA fragmentation (terminal deoxynu-cleotidyl transferase-mediated dUTP nick-end labeling). We observed in the sensorimotor cortex and cerebellum of ketamine-treated mice extensive apoptosis, which was clearly dose-dependent and present.

Original languageEnglish
Pages (from-to)231-244
Number of pages14
JournalJournal of Basic and Clinical Physiology and Pharmacology
Volume16
Issue number4
DOIs
StatePublished - 2005

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