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Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A 'central hub' in schizophrenia pathophysiology?
- Source :
- Schizophrenia research, vol. 176, no. 1, pp. 41-51
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Accumulating evidence points to altered GABAergic parvalbumin-expressing interneurons and impaired myelin/axonal integrity in schizophrenia. Both findings could be due to abnormal neurodevelopmental trajectories, affecting local neuronal networks and long-range synchrony and leading to cognitive deficits. In this review, we present data from animal models demonstrating that redox dysregulation, neuroinflammation and/or NMDAR hypofunction (as observed in patients) impairs the normal development of both parvalbumin interneurons and oligodendrocytes. These observations suggest that a dysregulation of the redox, neuroimmune, and glutamatergic systems due to genetic and early-life environmental risk factors could contribute to the anomalies of parvalbumin interneurons and white matter in schizophrenia, ultimately impacting cognition, social competence, and affective behavior via abnormal function of micro- and macrocircuits. Moreover, we propose that the redox, neuroimmune, and glutamatergic systems form a “central hub” where an imbalance within any of these “hub” systems leads to similar anomalies of parvalbumin interneurons and oligodendrocytes due to the tight and reciprocal interactions that exist among these systems. A combination of vulnerabilities for a dysregulation within more than one of these systems may be particularly deleterious. For these reasons, molecules, such as N-acetylcysteine, that possess antioxidant and anti-inflammatory properties and can also regulate glutamatergic transmission are promising tools for prevention in ultra-high risk patients or for early intervention therapy during the first stages of the disease.
- Subjects :
- 0301 basic medicine
Humans
Inflammation/immunology
Inflammation/metabolism
Interneurons/immunology
Interneurons/metabolism
Oligodendroglia/immunology
Oligodendroglia/metabolism
Oxidation-Reduction
Parvalbumins/immunology
Parvalbumins/metabolism
Receptors, N-Methyl-D-Aspartate/immunology
Receptors, N-Methyl-D-Aspartate/metabolism
Schizophrenia/immunology
Schizophrenia/metabolism
Development
Myelination
N-acetylcysteine
Oligodendrocytes
Oxidative stress
Parvalbumin interneurons
Receptors, N-Methyl-D-Aspartate
Article
White matter
03 medical and health sciences
Glutamatergic
Myelin
0302 clinical medicine
Interneurons
medicine
Biological Psychiatry
Neuroinflammation
Inflammation
biology
musculoskeletal, neural, and ocular physiology
Perineuronal net
medicine.disease
Oligodendroglia
Psychiatry and Mental health
Parvalbumins
030104 developmental biology
medicine.anatomical_structure
nervous system
Schizophrenia
biology.protein
GABAergic
Neuroscience
030217 neurology & neurosurgery
Parvalbumin
Subjects
Details
- ISSN :
- 09209964
- Volume :
- 176
- Database :
- OpenAIRE
- Journal :
- Schizophrenia Research
- Accession number :
- edsair.doi.dedup.....8adfb9f438b68070d8600fe2171d9a6a