Nitric Oxide, Free Radicals and Polyamines May Have a Role in the Membrane Pathology of Schizophrenia

Das, Indrajit; Ramchand, C.N.; Gliddon, A.; Hirsch, Steven R.

doi:10.1159/000026478

Cited by 26 publications

(7 citation statements)

References 10 publications

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“…Biochemical results also endorse the implication of NO in schizophrenia. In particular, low quantities of NO metabolites were noticed in plasma [ 33 , 34 , 35 ] and serum of first-episode, drug-naïve schizophrenics [ 36 , 37 , 38 ]. Bearing in mind that cognitive deficits is a typical feature of schizophrenics, lowering NO levels might indeed has severe repercussions for patients suffering from schizophrenia [ 27 ].…”

Section: No and Schizophreniamentioning

confidence: 99%

The Nitric Oxide (NO) Donor Sodium Nitroprusside (SNP) and Its Potential for the Schizophrenia Therapy: Lights and Shadows

Zoupa

Pitsikas

2021

Molecules

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Schizophrenia is a severe psychiatric disorder affecting up to 1% of the worldwide population. Available therapy presents different limits comprising lack of efficiency in attenuating negative symptoms and cognitive deficits, typical features of schizophrenia and severe side effects. There is pressing requirement, therefore, to develop novel neuroleptics with higher efficacy and safety. Nitric oxide (NO), an intra- and inter-cellular messenger in the brain, appears to be implicated in the pathogenesis of schizophrenia. In particular, underproduction of this gaseous molecule is associated to this mental disease. The latter suggests that increment of nitrergic activity might be of utility for the medication of schizophrenia. Based on the above, molecules able to enhance NO production, as are NO donors, might represent a class of compounds candidates. Sodium nitroprusside (SNP) is a NO donor and is proposed as a promising novel compound for the treatment of schizophrenia. In the present review, we intended to critically assess advances in research of SNP for the therapy of schizophrenia and discuss its potential superiority over currently used neuroleptics.

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Section: No and Schizophreniamentioning

confidence: 99%

The Nitric Oxide (NO) Donor Sodium Nitroprusside (SNP) and Its Potential for the Schizophrenia Therapy: Lights and Shadows

Zoupa

Pitsikas

2021

Molecules

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“…Several reports have targeted the levels of cerebral and peripheral PA in schizophrenia patients. Elevated blood concentrations of spermine and/or spermidine have been measured in treated schizophrenia patients[ 73 , 74 ] and in drug-naïve cases[ 75 ], whereby long-term neuroleptic treatment was shown to reduce spermine levels[ 75 , 76 ]. Also, increased concentrations of spermidine and total PA were detected in fibroblasts obtained from schizophrenia patients (reviewed in[ 11 ]).…”

Section: Pa Content In Tissues and Body Fluids In Schizophreniamentioning

confidence: 99%

“…Curiously, the opposite is the case as either increased blood and brain levels[ 73 - 75 ] or normal concentrations[ 65 ] of PA and ODC[ 81 , 85 , 87 ] have been reported for schizophrenia and animal disease models. Moreover, increased PA levels are not the result of neuroleptic treatment since anti-psychotics decrease PA concentrations in tissues and blood[ 75 , 76 ]. Thus, it seems unlikely that increased concentrations of spermine or other PAs contribute to schizophrenia pathology.…”

Section: Possible Impact Of Pa Pathway Abnormalities On Schizophrenia Pathologymentioning

confidence: 99%

Polyamines and polyamine-metabolizing enzymes in schizophrenia: Current knowledge and concepts of therapy

Bernstein¹,

Keilhoff²,

Laube³

et al. 2021

WJP

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Polyamines play preeminent roles in a variety of cellular functions in the central nervous system and other organs. A large body of evidence suggests that the polyamine pathway is prominently involved in the etiology and pathology of schizophrenia. Alterations in the expression and activity of polyamine metabolizing enzymes, as well as changes in the levels of the individual polyamines, their precursors and derivatives, have been measured in schizophrenia and animal models of the disease. Additionally, neuroleptic treatment has been shown to influence polyamine concentrations in brain and blood of individuals with schizophrenia. Thus, the polyamine system may appear to be a promising target for neuropharmacological treatment of schizophrenia. However, for a number of practical reasons there is currently only limited hope for a polyamine-based schizophrenia therapy.

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“…Several genes involved in polyamine metabolism have been shown to be altered in patients with schizophrenia 107,108 . Assessment and comparison of polyamine levels in psychiatric patients with schizophrenia and healthy controls have shown a significant increase in the concentration of polyamine oxidative enzymes in the blood of schizophrenic patients, 107,109–111 whereas results from skin fibroblast studies showed that polyamines were increased in antipsychotic‐treated patients, as compared to drug‐free patients 112 . In the human frontal cortex and hippocampus, no alteration was found in polyamines and ODC activity between patients with schizophrenia and healthy controls 113 .…”

Section: The Endogenous Antagonists Of the Nmdar In Schizophreniamentioning

confidence: 99%

Endogenous antagonists of N‐methyl‐d‐aspartate receptor in schizophrenia

Jorratt

Höschl

Ovsepian

2020

Alzheimer's & Dementia

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Schizophrenia is a chronic neuropsychiatric brain disorder that has devastating personal impact and rising healthcare costs. Dysregulation of glutamatergic neurotransmission has been implicated in the pathobiology of the disease, attributed largely to the hypofunction of the N‐methyl‐d‐aspartate (NMDA) receptor. Currently, there is a major gap in mechanistic analysis as to how endogenous modulators of the NMDA receptors contribute to the onset and progression of the disease. We present a systematic review of the neurobiology and the role of endogenous NMDA receptor antagonists in animal models of schizophrenia, and in patients. We discuss their neurochemical origin, release from neurons and glia with action mechanisms, and functional effects, which might contribute toward the impairment of neuronal processes underlying this complex pathological state. We consider clinical evidence suggesting dysregulations of endogenous NMDA receptor in schizophrenia, and highlight the pressing need in future studies and emerging directions, to restore the NMDA receptor functions for therapeutic benefits.

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Nitric Oxide, Free Radicals and Polyamines May Have a Role in the Membrane Pathology of Schizophrenia

Cited by 26 publications

References 10 publications

The Nitric Oxide (NO) Donor Sodium Nitroprusside (SNP) and Its Potential for the Schizophrenia Therapy: Lights and Shadows

The Nitric Oxide (NO) Donor Sodium Nitroprusside (SNP) and Its Potential for the Schizophrenia Therapy: Lights and Shadows

Polyamines and polyamine-metabolizing enzymes in schizophrenia: Current knowledge and concepts of therapy

Endogenous antagonists of N‐methyl‐d‐aspartate receptor in schizophrenia

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