Synaptic plasticity impairment and hypofunction of NMDA receptors induced by glutathione deficit: Relevance to schizophrenia

@article{Steullet2006SynapticPI,
  title={Synaptic plasticity impairment and hypofunction of NMDA receptors induced by glutathione deficit: Relevance to schizophrenia},
  author={Pascal Steullet and Hans Ch Neijt and Michel Cu{\'e}nod and Kim Q. Do},
  journal={Neuroscience},
  year={2006},
  volume={137},
  pages={807-819}
}

Glutathione Restores the Mechanism of Synaptic Plasticity in Aged Mice to That of the Adult

TLDR
It is concluded that aging leads to a reduced redox potential in hippocampal neurons, triggering impairments in LTP.

Synaptic NMDA receptor activity is coupled to the transcriptional control of the glutathione system

TLDR
It is shown that synaptic activity is coupled, via the NMDA receptor (NMDAR), to control of the glutathione antioxidant system, which tunes antioxidant capacity to reflect the elevated needs of an active neuron, guards against future increased demand and maintains redox balance in the brain.

NMDA-receptor inhibition and oxidative stress during hippocampal maturation differentially alter parvalbumin expression and gamma-band activity

TLDR
Although disturbances of PV-expression and gamma oscillations coexist in schizophrenia, they can arise from separate pathological processes.

The origin of NMDA receptor hypofunction in schizophrenia.

Glutamatergic Dysbalance and Oxidative Stress in In Vivo and In Vitro Models of Psychosis Based on Chronic NMDA Receptor Antagonism

TLDR
The combined in vivo and in vitro strategy allowed us to assess the implications of disturbed glutamate metabolism for the occurrence of oxidative stress and to investigate the effects of antipsychotics, suggesting that oxidative stress plays a minor role in this model than previously suggested.

Impairments in hippocampal synaptic plasticity following prenatal ethanol exposure are dependent on glutathione levels

TLDR
It is shown that depletion of the intracellular reserves of GSH with diethyl maleate reduces LTP in control male, but not female animals, mirroring the effects of PNEE, and that PnEE may cause reductions in LTP by reducing the intrACEllular pool of this endogenous antioxidant.

Impaired Attention and Synaptic Senescence of the Prefrontal Cortex Involves Redox Regulation of NMDA Receptors

TLDR
The results indicate that redox changes contribute to senescent synaptic function in vulnerable brain regions involved in age-related cognitive decline.

Redox Dysregulation Affects the Ventral But Not Dorsal Hippocampus: Impairment of Parvalbumin Neurons, Gamma Oscillations, and Related Behaviors

TLDR
A genetically compromised GSH synthesis affects the morphological and functional integrity of hippocampal parvalbumin-immunoreactive (PV-IR) interneurons, known to be affected in schizophrenia, leading to behavioral phenotypes related to psychiatric disorders.
...

References

SHOWING 1-10 OF 85 REFERENCES

Synaptic plasticity is impaired in rats with a low glutathione content

TLDR
The findings indicate that low content of glutathione can impair short‐term and long‐term mechanisms of synaptic plasticity and stress the importance of the redox balance in the normal function of brain circuitry.

Redox modulation of synaptic responses and plasticity in rat CA1 hippocampal neurons

TLDR
It is suggested that persistent, bidirectional changes in synaptic currents mediated by NMDA receptors cannot be evoked when these receptors are in an oxidized state, whereas NMDA-dependent LTP and LTD are still expressed by AMPA receptors.

Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo

TLDR
In cerebrospinal fluid of drug‐free schizophrenic patients, a significant decrease in the level of total glutathione (GSH) was observed, in keeping with the reported reduced level of its metabolite γ‐glutamylglutamine.

Regulation of NMDA Receptors by Neuregulin Signaling in Prefrontal Cortex

TLDR
This study suggests that both PLC/IP3R/Ca2+ and Ras/MEK/ERK (extracellular signal-regulated kinase) signaling pathways are involved in the neuregulin-induced reduction of NMDA receptor currents, which is likely through enhancing NR1 internalization via an actin-dependent mechanism.

Impairment of synaptic transmission by transient hypoxia in hippocampal slices: improved recovery in glutathione peroxidase transgenic mice.

TLDR
It is suggested that a moderate GPx increase can be sufficient to prevent irreversible functional damage produced by transient hypoxia in the hippocampus and to help maintain basic electrophysiological mechanisms involved in memory formation.

Frequency-dependent involvement of NMDA receptors in the hippocampus: a novel synaptic mechanism

TLDR
It is described how NMDA receptors can participate during high-frequency synaptic transmission in the hippocampus, their involvement during low-frequency transmission being greatly suppressed by Mg2+.
...