Glutamate theories of schizophrenia suggest that the disease is associated with a loss of NMDA receptors, specifically on GABAergic parvalbumin-expressing interneurons (PVIs), leading to changes in the excitation-inhibition balance in the prefrontal cortex (PFC). Oxidative stress contributes to the loss of PVI and the development of schizophrenia. Here, we investigated whether the glutathione precursor N-acetyl cysteine (NAC) can prevent changes in synaptic transmission at pyramidal cells and PVIs that result from developmental NMDAR blockade and how these changes are related to mitochondrial dysfunction in the PFCs of mice. Perinatal treatment with ketamine induced persistent changes in the reduced glutathione/oxidized glutathione (glutathione disulfide) ratio in the medial PFC, indicating long-lasting increases in oxidative stress. Perinatal ketamine treatment also reduced parvalbumin expression, and it induced a decline in mitochondrial membrane potential, as well as elevations in mitochondrial superoxide levels. At the level of synaptic function ketamine reduced inhibition onto layer 2/3 pyramidal cells and increased excitatory drive onto PVI, indicating long-lasting disruptions in the excitation-inhibition balance. These changes were accompanied by layer-specific alterations in NMDAR function in PVIs. All of these changes were mitigated by coadministration of NAC. In addition, NAC given only during late adolescence was also able to restore normal mitochondria function and inhibition at pyramidal cells. These results show that ketamine-induced alterations in PFC physiology correlate with cell type-specific changes in mitochondria function. The ability of NAC to prevent or restore these changes supports the usefulness of antioxidant supplementation in the treatment of schizophrenia.
Pubmed ID: 28819639 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.
View all literature mentionsAn independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
View all literature mentionsSoftware tool that detects peaks of any type, any shape, any direction, and any size for neuroscientists who are studying spontaneous activities. Allows detection of virtually any kind of peaks including spontaneous miniature synaptic currents and potentials, action potential spikes, calcium imaging peaks, amperometric peaks, ECG peaks etc. It includes the complex and multiple peak detection algorithm. Has post-detection analyses including essential plots and statistical parameters. Group Analysis provides specialized and detailed analysis options for action potentials, decay fitting, fEPSP/population spikes, amperometry, etc.
View all literature mentionsSoftware tool that detects peaks of any type, any shape, any direction, and any size for neuroscientists who are studying spontaneous activities. Allows detection of virtually any kind of peaks including spontaneous miniature synaptic currents and potentials, action potential spikes, calcium imaging peaks, amperometric peaks, ECG peaks etc. It includes the complex and multiple peak detection algorithm. Has post-detection analyses including essential plots and statistical parameters. Group Analysis provides specialized and detailed analysis options for action potentials, decay fitting, fEPSP/population spikes, amperometry, etc.
View all literature mentionsThis polyclonal targets parvalbumin
View all literature mentionsThis unknown targets CaMKII
View all literature mentionsThis unknown targets Rabbit IgG, F'2 Fragment Specific
View all literature mentionsFixed-stage microscope for electrophysiological research. Features include open design, noise reduction, 16x objective lens, and water dipping objective with depth induced aberration correction.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsImage processing software used to modify and clarify sample images for FluoView FV1000 range of confocal laser scanning microscopes and Fluoview FV1000MPE multiphoton excitation systems. The software incorporates high-dynamic-range imaging, minimized signal-to-noise ratios, partial stitching with multiarea time-lapse imaging, and channel unmixing. The software also allows users to select specific areas of the whole sample, which can stitched together.
View all literature mentionsMicroscope imaging software suite used with Nikon products. NIS-Elements includes software applications for advanced and standard research, documentation, confocal microscopy, and high-content analysis.
View all literature mentionsMus musculus with name CB6-Tg(Gad1-EGFP)G42Zjh/J from IMSR.
View all literature mentionsThis polyclonal targets parvalbumin
View all literature mentions