Increased oxidative stress in the anterior cingulate cortex of subjects with bipolar disorder and schizophrenia

Wang, Junfeng; Shao, Li; Sun, Xiujun; Young, L. Trevor

doi:10.1111/j.1399-5618.2009.00717.x

Cited by 226 publications

(142 citation statements)

References 58 publications

(55 reference statements)

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“…Finally, PNNs appear to be both protective against and altered by high levels of oxidative stress (Cabungcal et al, 2013a;Do et al, 2015;Morishita et al, 2015). Higher levels of oxidative stress have been reported in schizophrenia (Wang et al, 2009;Yao et al, 2006) and increased oxidative stress in an animal model results in lower WFA labeling of PNNs and alterations in γ-oscillations (Cabungcal et al, 2013a, b).…”

Section: Functional Consequences Of Lower Levels Of Pv and Pnn Componmentioning

confidence: 96%

Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

Enwright

Sanapala

Foglio

et al. 2016

Neuropsychopharmacol

188

139

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Alterations in cortical parvalbumin (PV)-containing neurons, including a reduced density of detectable neurons and lower PV levels, have frequently been reported in the dorsolateral prefrontal cortex (DLPFC) of schizophrenia subjects. Most PV neurons are surrounded by perineuronal nets (PNNs) and the density of PNNs, as detected by Wisteria floribunda agglutinin (WFA) labeling, has been reported to be lower in schizophrenia. However, the nature of these PNN alterations, and their relationship to disease-related changes in PV neurons, has not been assessed. Using confocal microscopy, we quantified the densities and fluorescence intensities of PV neurons and PNNs labeled with WFA or immunoreactive for the major PNN protein, aggrecan, in the DLPFC from schizophrenia and matched comparison subjects. In schizophrenia, the densities of PV cells and of PNNs were not altered; however, the fluorescence intensities of PV immunoreactivity in cell bodies and of WFA labeling and aggrecan immunoreactivity in individual PNNs around PV cells were lower. These findings indicate that the normal complements of PV cells and PNNs are preserved in schizophrenia, but the levels of PV protein and of individual PNN components, especially the carbohydrate moieties on proteoglycans to which WFA binds, are lower. Given the roles of PV neurons in regulating DLPFC microcircuits and of PNNs in regulating PV cellular physiology, the identified alterations in PV neurons and their PNNs could contribute to DLPFC dysfunction in schizophrenia.

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Section: Functional Consequences Of Lower Levels Of Pv and Pnn Componmentioning

confidence: 96%

Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

Enwright

Sanapala

Foglio

et al. 2016

Neuropsychopharmacol

188

139

View full text Add to dashboard Cite

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“…Parallel evidence of oxidative stress and altered antioxidant response is also found both in schizophrenia and in bipolar disorder (16,17). Oxidative stress and decreased levels of the endogenous antioxidant and redox regulator glutathione (GSH) are observed in the prefrontal cortex of patients (18)(19)(20). Therefore, redox dysregulation via impaired GSH synthesis (21,22) or abnormal function of proteins encoded by other susceptibility genes [i.e., proline dehydrogenase (oxidase) 1 (PRODH), disrupted in schizophrenia 1 (DISC1), D-amino acid oxidase activator (DAOA or G72), dystrobrevin binding protein 1 (DTNBP1)] (23)(24)(25)(26)(27) could, together with oxidative stress generated by environmental insults, contribute to the pathophysiology of these disorders (28,29).…”

mentioning

confidence: 94%

“…We assessed both the cumulative effect of chronic redox dysregulation and the effect of additional oxidative challenges applied at different ages. The anterior cingulate cortex (ACC) was chosen as a prefrontal area known to be affected and to display redox dysregulation in schizophrenia (20). In this study, we provide experimental evidence that the PNNs protect mature PV cells against oxidative stress.…”

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confidence: 99%

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Perineuronal nets protect fast-spiking interneurons against oxidative stress

Cabungcal

Steullet

Morishita

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

430

415

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A hallmark of schizophrenia pathophysiology is the dysfunction of cortical inhibitory GABA neurons expressing parvalbumin, which are essential for coordinating neuronal synchrony during various sensory and cognitive tasks. The high metabolic requirements of these fast-spiking cells may render them susceptible to redox dysregulation and oxidative stress. Using mice carrying a genetic redox imbalance, we demonstrate that extracellular perineuronal nets, which constitute a specialized polyanionic matrix enwrapping most of these interneurons as they mature, play a critical role in the protection against oxidative stress. These nets limit the effect of genetically impaired antioxidant systems and/or excessive reactive oxygen species produced by severe environmental insults. We observe an inverse relationship between the robustness of the perineuronal nets around parvalbumin cells and the degree of intracellular oxidative stress they display. Enzymatic degradation of the perineuronal nets renders mature parvalbumin cells and fast rhythmic neuronal synchrony more susceptible to oxidative stress. In parallel, parvalbumin cells enwrapped with mature perineuronal nets are better protected than immature parvalbumin cells surrounded by less-condensed perineuronal nets. Although the perineuronal nets act as a protective shield, they are also themselves sensitive to excess oxidative stress. The protection might therefore reflect a balance between the oxidative burden on perineuronal net degradation and the capacity of the system to maintain the nets. Abnormal perineuronal nets, as observed in the postmortem patient brain, may thus underlie the vulnerability and functional impairment of pivotal inhibitory circuits in schizophrenia.critical period | extracellular matrix | glutamate cysteine ligase | glutathione | neuronal synchronization F ast-spiking interneurons expressing parvalbumin (PV) constitute a subpopulation of GABA cells that control the output of principal neurons and are necessary for fast rhythmic neuronal synchrony, facilitating information processing during cognitive tasks (1, 2). To coordinate the activity of neuronal assemblies, PV cells are interconnected by both chemical and electrical synapses, have the capacity to fire at high frequency without adaptation, and selectively position inhibitory synaptic terminals onto the cell body and axon initial segment of their target neurons. Fast-spiking properties consequently impose high metabolic demand and increased mitochondrial density, which renders PV cells, but not other interneurons such as calretinin and calbindin cells, particularly sensitive to oxidative stress (3). For instance, ketamine induces superoxide overproduction that strongly impairs PV cells (i.e., loss of normal phenotype including PV immunoreactivity but without cell death) (4, 5). Moreover, severe environmental stressors produce oxidative stress in the brain and impair PV cells (6)(7)(8). Postmortem studies reveal PV-cell anomalies in individuals with schizophrenia or bipolar disorder (9-11). ...

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“…The biosynthesis of catecholamines occurs in tissues rich in ascorbic acid like the brain and the adrenal gland. In addition having vitamin C in the diet is associated with a reduced level of major changes in cognitive performance [31,32]. Vitamin C is involved in neuronal transmission and neurotransmitter metabolism.…”

Section: Effect Of Micronutrient On Depressionmentioning

confidence: 99%

The Role of Micronutrient for Depressed Patients

Demelash¹

2017

J Neuropsychopharmacol Mental Health

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Majority of people are not aware of the relation between nutrition and depression. Depression is mostly resulted from an imbalance in brain chemical that can be due to more typically thought of as strictly biochemical-based or emotionally-rooted. As a result, nutrition can play a key role in the onset as well as severity and duration of depression. Several micronutrient deficiencies adversely affect the brain and hence could aggravate mental disorders. It is important that proper attention to diet, and, when indicated, appropriate supplementation with vitamin C, folic acid, niacin, thiamine, iron, zinc, magnesium , potassium and sodium and omega-3 fatty acids. As the brain chemical (neurotransmitters) are made from chemical precursors, usually from an amino acid (protein) and other micronutrients (vitamin and minerals), it is clear to understand how deficiencies of these nutrients could lead to changes in the pattern of brain chemical neurotransmitter production leading to mental illness like depression.

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Increased oxidative stress in the anterior cingulate cortex of subjects with bipolar disorder and schizophrenia

Abstract: Oxidative damage in the brain may contribute in part to the pathological process in BD and schizophrenia. This finding also suggests antioxidative stress as a probable alternative approach to the pharmacological treatment of these psychiatric disorders.

Cited by 226 publications

References 58 publications

Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia

Perineuronal nets protect fast-spiking interneurons against oxidative stress

The Role of Micronutrient for Depressed Patients

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