Minocycline exacerbates apoptotic neurodegeneration induced by the NMDA receptor antagonist MK-801 in the early postnatal mouse brain.
NMDA receptor (NMDAR) antagonists induce in perinatal rodent cortical apoptosis and protracted schizophrenia-like alterations ameliorated by antipsychotic treatment. The broad-spectrum antibiotic minocycline elicits antipsychotic and neuroprotective effects. Here we tested, if minocycline protects also against apoptosis triggered by the NMDAR antagonist MK-801 at postnatal day 7. Surprisingly, minocycline induced widespread cortical apoptosis and exacerbated MK-801-triggered cell death. In some areas such as the subiculum, the pro-apoptotic effect of minocycline was even more pronounced than that elicited by MK-801. These data reveal among antipsychotics unique pro-apoptotic properties of minocycline, raising concerns regarding consequences for brain development and the use in children.
Division of Pediatric Endocrinology, University Children's Hospital Heidelberg, Heidelberg, Germany.
Ioana
I
Inta
Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, Central Institute for Mental Health Mannheim, University of Heidelberg, Heidelberg, Germany.
Miriam A
MA
Vogt
Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, Central Institute for Mental Health Mannheim, University of Heidelberg, Heidelberg, Germany.
Anne S
AS
Vogel
Division of Pediatric Endocrinology, University Children's Hospital Heidelberg, Heidelberg, Germany.
Markus
M
Bettendorf
Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, Central Institute for Mental Health Mannheim, University of Heidelberg, Heidelberg, Germany.
Peter
P
Gass
Department of Psychiatry and Psychotherapy, Medical Faculty Mannheim, Central Institute for Mental Health Mannheim, University of Heidelberg, Heidelberg, Germany. Dragos.Inta@zi-mannheim.de.
Dragos
D
Inta
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000900:Anti-Bacterial Agents; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D008911:Minocycline
Caspase-3; MK-801; Minocycline; Neurodevelopment; Neurotoxicity; Schizophrenia