Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology?

@article{Steullet2016RedoxDN,
  title={Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology?},
  author={Pascal Steullet and J. H. Cabungcal and Aline Monin and Daniella Dwir and Patriot O′Donnell and Michel Cu{\'e}nod and Kim Quang Do},
  journal={Schizophrenia Research},
  year={2016},
  volume={176},
  pages={41-51}
}
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Oxidative stress may result from dysregulation of systems typically affected in schizophrenia, including glutamatergic, dopaminergic, immune and antioxidant signaling, and redox dysregulation has successfully been targeted to protect PVIs with antioxidants/redox regulators across several animal models.

Potential Roles of Redox Dysregulation in the Development of Schizophrenia

A developmental redox dysregulation leads to spatio-temporal deficit of parvalbumin neuron circuitry in a schizophrenia mouse model

MMP9/RAGE pathway overactivation mediates redox dysregulation and neuroinflammation, leading to inhibitory/excitatory imbalance: a reverse translation study in schizophrenia patients

MMP9 inhibition appears to be able to interrupt the vicious circle that maintains the long-lasting deleterious effects of the reciprocal interaction between oxidative stress and neuroinflammation, impacting on PVI/PNN integrity.

Oxidative stress, prefrontal cortex hypomyelination and cognitive symptoms in schizophrenia

The redox-induced prefrontal OPC-dysfunctioning hypothesis provides a novel neurobiological framework for the aetiology of SZ cognitive symptoms and could have important implications for the development of new (combined) antioxidant- and promyelination-based strategies to treat the cognitive symptoms in SZ.

Interneuron epigenomes during the critical period of cortical plasticity: Implications for schizophrenia

Deletion of the Mitochondrial Matrix Protein CyclophilinD Prevents Parvalbumin Interneuron Dysfunctionand Cognitive Deficits in a Mouse Model of NMDA Hypofunction

Mice deficient for the mitochondrial matrix protein cyclophilin D (CypD) show robust protection from PVI dysfunction following perinatal NMDAR blockade, highlighting how mitochondrial activity may play an integral role in modulating PVI-mediated cognitive processes.

Biomarkers in Early Psychosis

  • Psychology, Biology
  • 2015
In gclm‐/‐ mice, an additional stress during youth induces a prefrontal oxidative stress involving specifically PVIs deficits, an anomaly persisting into adulthood, while the application of the antioxidant and GSH precursor N‐acetyl‐cysteine throughout life prevents this deficit.

Deletion of the mitochondrial matrix protein cyclophilin-D prevents parvalbumin interneuron dysfunction and cognitive deficits in a mouse model of NMDA hypofunction

It is shown that mice deficient for the mitochondrial matrix protein cyclophilin D show robust protection from PVI dysfunction following perinatal NMDAR-blockade, and this data highlights how mitochondrial activity may play an integral role in modulating PVI-mediated cognitive processes.
...

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