Single-dose ketamine administration induces apoptosis in neonatal mouse brain
| Autor: | Yevgeney Tendler, Vered Gazit, Yeshayahu Katz, Michael Rudin, Ron Ben-Abraham, Vadim Tashlykov |
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| Rok vydání: | 2006 |
| Předmět: |
Cerebellum
medicine.medical_specialty Silver Staining Physiology Apoptosis Mice In Situ Nick-End Labeling Internal medicine Drug Discovery Medicine Animals Ketamine Receptor Coloring Agents Hematoxylin Pharmacology Mice Inbred ICR Behavior Animal business.industry Brain General Medicine Organ Size medicine.anatomical_structure Endocrinology Animals Newborn Nerve Degeneration NMDA receptor DNA fragmentation Eosine Yellowish-(YS) Righting reflex business Excitatory Amino Acid Antagonists medicine.drug |
| Zdroj: | Journal of basic and clinical physiology and pharmacology. 16(4) |
| ISSN: | 0792-6855 |
| Popis: | UNLABELLED 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 deoxynucleotidyl 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 even after a low dose of ketamine (5 mg/kg). The most prominent apoptotic damage was detected 72 h post-injection (P < 0.001 vs control), at doses ranging from 10 to 40 mg/kg. After 7 d the number of neurodegenerative neurons, at doses ranging from 5 to 40 mg/kg, remained significantly high. The brain weight was comparable to that of untreated control mice and no gross neurobehavioral effects in the righting reflex test or alteration in the pattern of behavior was observed. The results indicate that the administration of ketamine in a clinically relevant single dose triggers long-lasting neuronal apoptosis in certain brain areas of neonatal mice. IMPLICATIONS The administration of ketamine in a clinically relevant single dose to 7-d-old mice induced apoptosis in the sensorimotor cortex and cerebellum. This effect was dose-dependent and long lasting. |
| Databáze: | OpenAIRE |
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