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A lack of GluN2A-containing NMDA receptors confers a vulnerability to redox dysregulation: Consequences on parvalbumin interneurons, and their perineuronal nets
- Source :
- Neurobiology of disease, vol. 109, no. Pt A, pp. 64-75, Neurobiology of Disease, Vol 109, Iss, Pp 64-75 (2018)
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- The GluN2A subunit of NMDA receptors (NMDARs) plays a critical role during postnatal brain development as its expression increases while Glun2B expression decreases. Mutations and polymorphisms in GRIN2A gene, coding for GluN2A, are linked to developmental brain disorders such as mental retardation, epilepsy, schizophrenia. Published data suggest that GluN2A is involved in maturation and phenotypic maintenance of parvalbumin interneurons (PVIs), and these interneurons suffer from a deficient glutamatergic neurotransmission via GluN2A-containing NMDARs in schizophrenia. In the present study, we find that although PVIs and their associated perineuronal nets (PNNs) appear normal in anterior cingulate cortex of late adolescent/young adult GRIN2A KO mice, a lack of GluN2A delays PNN maturation. GRIN2A KO mice display a susceptibility to redox dysregulation as sub-threshold oxidative stress and subtle alterations in antioxidant systems are observed in their prefrontal cortex. Consequently, an oxidative insult applied during early postnatal development increases oxidative stress, decreases the number of parvalbumin-immunoreactive cells, and weakens the PNNs in KO but not WT mice. These effects are long-lasting, but preventable by the antioxidant, N-acetylcysteine. The persisting oxidative stress, deficit in PVIs and PNNs, and reduced local high-frequency neuronal synchrony in anterior cingulate of late adolescent/young adult KO mice, which have been challenged by an early-life oxidative insult, is accompanied with microglia activation. Altogether, these indicate that a lack of GluN2A-containing NMDARs alters the fine control of redox status, leading to a delayed maturation of PNNs, and conferring vulnerability for long-term oxidative stress, microglial activation, and PVI network dysfunction.
- Subjects :
- Male
0301 basic medicine
Dopamine
Prefrontal Cortex
Parvalbumin interneuron
Neurotransmission
medicine.disease_cause
Gyrus Cinguli
Receptors, N-Methyl-D-Aspartate
Anterior cingulate cortex
lcsh:RC321-571
03 medical and health sciences
Glutamatergic
0302 clinical medicine
Interneurons
Glutahione
medicine
Animals
Prefrontal cortex
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Perineuronal net
Mice, Knockout
biology
Peroxiredoxin
Acetylcysteine
Extracellular Matrix
Mice, Inbred C57BL
Oxidative Stress
Parvalbumins
030104 developmental biology
medicine.anatomical_structure
nervous system
Neurology
Dopamine/metabolism
Female
Gyrus Cinguli/growth & development
Gyrus Cinguli/metabolism
Gyrus Cinguli/physiology
Interneurons/metabolism
Microglia/metabolism
Oxidation-Reduction
Parvalbumins/metabolism
Prefrontal Cortex/metabolism
Receptors, N-Methyl-D-Aspartate/genetics
Receptors, N-Methyl-D-Aspartate/metabolism
Microglia
Mouse
Oscillations
Oxidative stress
Sulfiredoxin
biology.protein
GRIN2A
Neuroscience
030217 neurology & neurosurgery
Parvalbumin
Subjects
Details
- ISSN :
- 09699961
- Volume :
- 109
- Database :
- OpenAIRE
- Journal :
- Neurobiology of Disease
- Accession number :
- edsair.doi.dedup.....107ea94cae8ebf7363d9a8bcbe1d5971