Abstract
Brain injury during the last trimester to the first 1–4 years in humans is now thought to trigger an array of intellectual and emotional problems later in life, including disorders such as schizophrenia. In adult schizophrenic brains, there is a specific loss of neurons that co-express glutamic acid decarboxylase-parvalbumin (GAD67-PV). Loss of this phenotype is thought to occur in mature animals previously exposed to N-methyl-d-aspartate receptor (NMDAR) antagonists during late gestation or at postnatal day 7 (P7). However, in similarly treated animals, we have previously shown that GAD67 and PV are unaltered in the first 24 h. To more precisely define when changes in these markers first occur, we exposed rat pups (P7 or P6–P10) to the NMDAR antagonist MK801 and at P11 co-stained brain sections for GAD67 or PV. In the cingulate cortex, we found evidence for a reduction in PV (GAD67 levels were very low to undetectable). In contrast, in the somatosensory cortex, we found that expression of GAD67 was reduced, but PV remained stable. Further, repeated but not single doses of MK801 were necessary to see such changes. Thus, depending on the region, NMDAR antagonism appears to influence expression of PV or GAD67, but not both. These observations could not have been predicted by previous studies and raise important questions as to how the GAD67-PV phenotype is lost once animals reach maturity. More importantly, such differential effects may be of great clinical importance, given that cognitive deficits are seen in children exposed to anesthetics that act by blocking the NMDAR.
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Acknowledgments
This work was supported by NIH RO1 NS051632. Injections, perfusions and histology by CPT and CL; image capture, processing and quantification by all authors (except CPT); figure construction by all authors; manuscript preparation by CPT.
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Turner, C.P., DeBenedetto, D., Ware, E. et al. Postnatal exposure to MK801 induces selective changes in GAD67 or parvalbumin. Exp Brain Res 201, 479–488 (2010). https://doi.org/10.1007/s00221-009-2059-z
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DOI: https://doi.org/10.1007/s00221-009-2059-z