Ketamine-Induced Loss of Phenotype of Fast-Spiking Interneurons Is Mediated by NADPH-Oxidase
SciencePublished 6 December 2007
M. Margarita Behrens, Sameh S. Ali, Diep N. Dao, Jacinta Lucero, Grigoriy Shekhtman, Kevin L. Quick
Citations590
SJR quartileQ1
SJR score10.42
SNIP6.62
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TL;DR
It is shown that exposure of mice to ketamine induced a persistent increase in brain superoxide due to activation in neurons of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which suggests that NADPH oxidase may represent a novel target for the treatment of ketamine-induced psychosis.
Abstract
Abuse of the dissociative anesthetic ketamine can lead to a syndrome indistinguishable from schizophrenia. In animals, repetitive exposure to this N-methyl-d-aspartate-receptor antagonist induces the dysfunction of a subset of cortical fast-spiking inhibitory interneurons, with loss of expression of parvalbumin and the gamma-aminobutyric acid-producing enzyme GAD67. We show here that exposure of mice to ketamine induced a persistent increase in brain superoxide due to activation in neurons of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Decreasing superoxide production prevented the effects of ketamine on inhibitory interneurons in the prefrontal cortex. These results suggest that NADPH oxidase may represent a novel target for the treatment of ketamine-induced psychosis.
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128 Citations2006K.M. Day-Wilson, Declan N.C. Jones +3 more
The robust reduction in prefrontal cortical volume observed in isolation-reared rats, in the absence of reductions in total neuron number, suggest that there is a loss of volume of the neuropil, which supports the construct validity of this model.
European Journal of NeuroscienceDecrease in parvalbumin‐expressing neurons in the hippocampus and increased phencyclidine‐induced locomotor activity in the rat methylazoxymethanol (MAM) model of schizophrenia
128 Citations2005Silke Penschuck, Peter Flagstad +3 more
The developmental MAM‐GD17 model reproduces key neurochemical and behavioural features that reflect cortical and subcortical dysfunction in schizophrenia, and could be a useful tool in the development of new antipsychotic drugs.
DevelopmentMultidirectional and multizonal tangential migration of GABAergic interneurons in the developing cerebral cortex
128 Citations2006Daisuke H. Tanaka, K. Maekawa +3 more
Time-lapse imaging and in vivo labelling indicated that MZ cortical interneurons undergo a second phase of tangential migration in all directions and over long distances, after reaching the cortex by dorsomedial tangential Migration.
NeuropsychopharmacologySpatial Memory Deficits Induced by Perinatal Treatment of Rats with PCP and Reversal Effect of D-Serine
126 Citations2004Janne Damm Andersen, Bruno Pouzet
It is suggested that this model mimics some of the cognitive deficits of patients with schizophrenia and might be appropriate for the screening of putative antipsychotic agents for the treatment of these cognitive deficits.
Schizophrenia ResearchAlterations of hippocampal and prefrontal GABAergic interneurons in an animal model of psychosis induced by NMDA receptor antagonism
124 Citations2007I Braun, Just Genius +4 more
Data show that a prolonged application of low-dose NMDA receptor antagonist could, in part, mimic some neuropathologic findings in human schizophrenia, thus strengthening the idea that (sub-) chronicNMDA receptor antagonism in animals is a viable approach in mimicking aspects of schizophrenia.
Annals of the New York Academy of SciencesPostnatal Development of Prefrontal Inhibitory Circuits and the Pathophysiology of Cognitive Dysfunction in Schizophrenia
124 Citations2004David A. Lewis, Dianne A. Cruz +2 more
The role that GABA‐mediated inhibition in the dorsal lateral prefrontal cortex (DLPFC) plays in regulating working memory, a core cognitive process that matures late and that is disturbed in schizophrenia, is reviewed.
PsychopharmacologyPrenatal exposure to an NMDA receptor antagonist, MK-801 reduces density of parvalbumin-immunoreactive GABAergic neurons in the medial prefrontal cortex and enhances phencyclidine-induced hyperlocomotion but not behavioral sensitization to methamphetamine in postpubertal rats
118 Citations2007Tomohiro Abekawa, Koki Ito +2 more
Findings suggest that prenatal blockade of NMDA receptors disrupts GABAergic neurodevelopment in medial prefrontal cortex, and that this disruption of GABAergic development may be related to the enhancement of the locomotion-inducing effect of PCP in postpubertal but not juvenile offspring.
MutagenesisSubcellular compartmentalization of glutathione: Correlations with parameters of oxidative stress related to genotoxicity
118 Citations2006Richard M. Green, M. Graham +3 more
The findings highlight the critical roles of the mitochondrial and nuclear GSH pools in protecting cellular components, particularly DNA, from oxidative modification and the genotoxic potential of compounds that deplete GSH.
Journal of NeurophysiologyProlonged Exposure to NMDAR Antagonist Suppresses Inhibitory Synaptic Transmission in Prefrontal Cortex
110 Citations2008Yuchun Zhang, M. Margarita Behrens +1 more
Schizophrenia ResearchRationale for the study of early intervention
105 Citations2001Richard Jed Wyatt, Ioline D. Henter
The findings presented set the stage for early and even earlier formal intervention studies, where the potential benefits are thought to outweigh the potential risks.
Journal of Pharmacology and Experimental TherapeuticsBlockade of Phencyclidine-Induced Cortical Apoptosis and Deficits in Prepulse Inhibition by M40403, a Superoxide Dismutase Mimetic
98 Citations2003Cheng Wang, Justin McInnis +7 more
Perinatal PCP treatment leads to long-lasting changes in the pathway(s), leading to cell death and behavioral deficits, and that the superoxide radical plays a critical role in the underlying mechanism.
Physiology & BehaviorIndividual Housing From Rearing Modifies the Performance of Young Rats on the Elevated Plus-Maze Apparatus
89 Citations1996NELCI LOPES DA SILVA, Vânia Maria Moraes Ferreira +2 more
The results suggest that 60-day-old rats deprived of playfighting experience high basal anxiety levels and also that rearing conditions (isolated or grouped) are able to interact with both anxiolytic and anxiogenic effects of experimental drugs.
NeuronOxygen or glucose deprivation-induced neuronal injury in cortical cell cultures is reduced by tetanus toxin
89 Citations1992Hannah Monyer, Rona G. Giffard +4 more
With prolonged exposure periods, the neuroprotective efficacy of tetanus toxin was comparable to that of NMDA receptor antagonists, suggesting presynaptic inhibition of Ca(2+)-dependent glutamate release may be a valuable approach to attenuating hypoxic-ischemic brain injury.
NeuroscienceRegion specific changes in forebrain 5-hydroxytryptamine1a and 5-hydroxytryptamine2a receptors in isolation-reared rats: an in vitro autoradiography study
86 Citations2003Mark Preece, Jeffrey W. Dalley +3 more
It is demonstrated that isolation-rearing produces significant effects on forebrain 5-HT(1A) and 5- HT(2A) receptor densities in the adult rat, and it is hypothesised that altered serotonergic function, particularly in the hippocampus and prefrontal cortex, may underlie some of the behavioural abnormalities associated with isolation- rearing.
SynapseAcute and delayed effects of phencyclidine upon mRNA levels of markers of glutamatergic and GABAergic neurotransmitter function in the rat brain
84 Citations2002Susan Cochran, Masatake Fujimura +2 more
Results indicate that the glutamatergic (group I metabotropic glutamate receptors) and GABAergic (parvalbumin‐containing interneurones) neurotransmitter systems are differentially modulated in a region‐ and time‐dependent manner by exposure to phencyclidine.
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