Role of astrocytes in alterations of glutamatergic neurotransmission in schizophrenia

Kolomeets, Natalya S.

doi:10.17116/jnevro201511511110-117

Cited by 3 publications

(1 citation statement)

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“…The NMDAR function is modulated by redox systems through the forming of disulfide bonds in receptor subunits that reduce NMDAR conductivity [ 22 ]. Astrocytic abnormalities in schizophrenia include disorders of glutamate reuptake, recycling, and turnover of endogenous NMDAR ligands [ 23 ]. The NMDAR hypofunction leads to cortical oxidative stress, GSH deficiency, and decreased activity of the thioredoxin/peroxiredoxin system through transcriptional control of several critical antioxidant genes [ 24 ].…”

Section: Oxidative Stress In the Central Nervous Systemmentioning

confidence: 99%

Oxidative Stress‐Related Mechanisms in Schizophrenia Pathogenesis and New Treatment Perspectives

Ermakov

Dmitrieva

Parshukova

et al. 2021

Oxidative Medicine and Cellular Longevity

137

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Schizophrenia is recognized to be a highly heterogeneous disease at various levels, from genetics to clinical manifestations and treatment sensitivity. This heterogeneity is also reflected in the variety of oxidative stress-related mechanisms contributing to the phenotypic realization and manifestation of schizophrenia. At the molecular level, these mechanisms are supposed to include genetic causes that increase the susceptibility of individuals to oxidative stress and lead to gene expression dysregulation caused by abnormal regulation of redox-sensitive transcriptional factors, noncoding RNAs, and epigenetic mechanisms favored by environmental insults. These changes form the basis of the prooxidant state and lead to altered redox signaling related to glutathione deficiency and impaired expression and function of redox-sensitive transcriptional factors (Nrf2, NF-κB, FoxO, etc.). At the cellular level, these changes lead to mitochondrial dysfunction and metabolic abnormalities that contribute to aberrant neuronal development, abnormal myelination, neurotransmitter anomalies, and dysfunction of parvalbumin-positive interneurons. Immune dysfunction also contributes to redox imbalance. At the whole-organism level, all these mechanisms ultimately contribute to the manifestation and development of schizophrenia. In this review, we consider oxidative stress-related mechanisms and new treatment perspectives associated with the correction of redox imbalance in schizophrenia. We suggest that not only antioxidants but also redox-regulated transcription factor-targeting drugs (including Nrf2 and FoxO activators or NF-κB inhibitors) have great promise in schizophrenia. But it is necessary to develop the stratification criteria of schizophrenia patients based on oxidative stress-related markers for the administration of redox-correcting treatment.

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Section: Oxidative Stress In the Central Nervous Systemmentioning

confidence: 99%