Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6272683 | Neuroscience | 2015 | 10 Pages |
Abstract
Anesthetic doses of ketamine induce apoptosis, as well as gene expression of activity-dependent neuroprotective protein (ADNP), a putative homeodomain transcription factor in rat pups (P7). This study investigated if ketamine induced ADNP protein in a dose-dependent manner in vitro and in vivo using primary cultures of cortical neurons and neonatal pups (P7). In vivo immunohistochemistry demonstrated a sub-anesthetic dose of ketamine increased ADNP in the somatosensory cortex (SCC) which was previously identified to be damaged by repeated exposure to anesthetic doses of ketamine. Administration of low-dose ketamine prior to full sedation prevented caspase-3 activation in the hippocampus and SCC. Primary cultures of cortical neurons treated with ketamine (10 μM-10 mM) at 3 days-in vitro (3 DIV) displayed a concentration-dependent decrease in expanded growth cones. Furthermore, neuronal production and localization of ADNP varied as a function of both ketamine concentration and length of exposure. Taken together, these data support the model that ADNP induction may be partially responsible for the efficacy of a low-dose ketamine pre-treatment in preventing ketamine-induced neuronal cell death.
Keywords
ADNPMK801AASSPFANMDAHBSSDAPIN-methyl-d-aspartateAC3BCAPBSTSSCPSDADNFDICPBSHEPESFITCNAP4′,6-diamidino-2-phenylindole4-(2-hydroxyethyl)-1-piperazineethanesulfonic acidAutism spectrum disorderbicinchoninic aciddizocilpineDIVactivity-dependent neurotrophic factorfluorescein isothiocyanateSomatosensory cortexPhosphate-buffered salineHank’s balanced salt solutionGrowth conesASDCortical neuronsparaformaldehydeActivity-dependent neuroprotective proteinpost-synaptic density protein 95Ketaminedifferential interference contrast
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Authors
B.P. Brown, S.C. Kang, K. Gawelek, R.A. Zacharias, S.R. Anderson, C.P. Turner, J.K. Morris,