The biochemical womb of schizophrenia: A review

Gaur, Navendu; Gaur, Mragank; Sharma, Praveen; Dadheech, Gora; Mishra, Saumya

doi:10.1007/s12291-008-0071-x

Cited by 18 publications

(17 citation statements)

References 208 publications

(170 reference statements)

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“…Serotonin receptors, especially 5‐HT 2A Rs and 5‐HT 1A Rs, play an important role in the therapeutic and/or side‐effect profiles of atypical antipsychotics (Gaur et al . ). Recently, the 5‐HT 1A R has been considered a promising additional target for antipsychotic treatment.…”

Section: Discussionmentioning

confidence: 97%

“…Considerable evidence has indicated that it is actually the balance between the properties of D 2 Rs and 5‐HT 1A Rs that has a profound influence on the profile of action of these drugs in preclinical models (Newman‐Tancredi ); however, these actions are also influenced by additional interactions at other receptor subtypes, such as 5‐HT 2A / 2C , mGluR2/3, and NMDA (Gaur et al . ; Meltzer and Huang ; Meltzer and Massey ). The association of D 2 Rs and 5‐HT 1A Rs in functional heteromers that exhibit properties distinct from those of either constituent GPCR may significantly modify the function of both proteins.…”

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confidence: 99%

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Dopamine D₂ and serotonin 5‐HT_1A receptor interaction in the context of the effects of antipsychotics – in vitro studies

Łukasiewicz

Błasiak

Szafran-Pilch

et al. 2016

Journal of Neurochemistry

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The serotonin 5-HT 1A receptor (5-HT 1A R) and dopamine D 2 receptor (D 2 R) have been implicated as important sites of action in antipsychotics. Several lines of evidence indicate the key role of G protein-coupled receptors (GPCRs) heteromers in pathophysiology of schizophrenia and highlight these complexes as novel drug targets. Because heterodimers can form only on those cells co-expressing constituent receptors, they present a target of high pharmacological specificity in the context of biochemical effects induced by antipsychotic drugs. In studies conducted in the HEK 293 cell line, we demonstrated that 5-HT 1A R and D 2 R are able to form constitutive heterodimers, and antipsychotic drugs (clozapine, olanzapine, aripiprazole, and lurasidone) enhanced this process, with clozapine being most effective. Various functional tests (cAMP and IP 1 as well as ERK activation) indicated that the drugs had different effects on signal transduction by the heteromer. Interestingly, co-incubation of heterodimer-expressing HEK 293 cells with clozapine and the 5-HT 1A R agonist 8-OH DPAT potentiated post-synaptic effects, especially with respect to ERK activation. Our results indicate that the D 2 -5-HT 1A complex possesses biochemical, pharmacological, and functional properties distinct from those of mono-and homomers. This result has implications for the development of improved pharmacotherapy for schizophrenia or other disorders (activating the heteromer might be cognitive enhancing, since it is expressed in frontal cortex) through the specific targeting of heterodimers.

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Dopamine D₂ and serotonin 5‐HT_1A receptor interaction in the context of the effects of antipsychotics – in vitro studies

Łukasiewicz

Błasiak

Szafran-Pilch

et al. 2016

Journal of Neurochemistry

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“…Alteration in the optimum activities of antioxidant enzymes [212][213][214] and related parameters of lipid peroxidation [215,216] in blood have been detected in schizophrenics. Brain contains large amount of unsaturated fatty acids, catecholamines and monoamines, which are the target molecules for lipid peroxidation [217,218]. Brain is rich in iron containing compounds and thus it is an easy target for lipid peroxidation through the formation of hydroxyl radicals.…”

Section: Vitamin C and Neurodegenerative Disordersmentioning

confidence: 99%

Vitamin C in Disease Prevention and Cure: An Overview

et al. 2013

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The recognition of vitamin C is associated with a history of an unrelenting search for the cause of the ancient haemorrhagic disease scurvy. Isolated in 1928, vitamin C is essential for the development and maintenance of connective tissues. It plays an important role in bone formation, wound healing and the maintenance of healthy gums. Vitamin C plays an important role in a number of metabolic functions including the activation of the B vitamin, folic acid, the conversion of cholesterol to bile acids and the conversion of the amino acid, tryptophan, to the neurotransmitter, serotonin. It is an antioxidant that protects body from free radical damage. It is used as therapeutic agent in many diseases and disorders. Vitamin C protects the immune system, reduces the severity of allergic reactions and helps to fight off infections. However the significance and beneficial effect of vitamin C in respect to human disease such as cancer, atherosclerosis, diabetes, neurodegenerative disease and metal toxicity however remains equivocal. Thus further continuous uninterrupted efforts may open new vistas to understand its significance in disease management.

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“…The dopamine hypothesis of SCZ is a widely known theory, which attempts to account for the pathophysiology of SCZ. Dopamine, in addition to carrying out roles as a neurotransmitter, is also highly linked to processes of oxidative stress and excitotoxicity associated with neurodegeneration [85]. Nishioka and Arnold (2004) found evidence of oxidative DNA damage in the hippocampus of chronic patients with SCZ [47].…”

Section: 3 Future Directionsmentioning

confidence: 99%

Β-Amyloid Burden is Not Associated with Cognitive Impairment in Schizophrenia: A Systematic Review

Chung

Nakajima

Plitman

et al. 2016

The American Journal of Geriatric Psychiatry

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Current literature suggests that the pathology of schizophrenia (SCZ) has developmental origins. However, the neurodevelopmental theory of SCZ cannot solely explain several progressive neurodegenerative processes in the illness. There is evidence of accelerated cognitive decline and increased risk of developing dementia in elderly patients with SCZ. Investigating beta-amyloid (Aβ) as a measure of neurodegeneration, we conducted a systematic review focusing on Aβ in patients with SCZ. An OVID literature search using PsychINFO, Medline and Embase database was conducted, looking for studies that compared Aβ levels between patients with SCZ and either elderly controls, patients with AD, or patients with other psychiatric illnesses. Among 14 identified studies, 11 compared Aβ levels between SCZ and elderly controls, seven between SCZ and AD, three between SCZ and other psychiatric illnesses. As a result, no evidence was found suggesting that Aβ levels differ in patients with SCZ from elderly controls or patients with other psychiatric illnesses. All of the seven studies reported lower cortical Aβ levels in patients with SCZ than patients with AD. Furthermore, three out of the four studies, which investigated the relationship between Aβ levels and cognitive impairment in SCZ, observed no association between two factors. The limitations of the included studies are small sample sizes, the inclusion of CSF Aβ or postmortem plaques rather than cortical Aβ assessment in-vivo, and the investigation of different brain regions. In conclusion, Aβ deposition is not associated with cognitive decline in late-life SCZ. Future studies should investigate other neurodegenerative indicators such as oxidative stress and apoptosis dysregulation in SCZ to better understand the pathophysiological mechanisms underlying this illness.

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The biochemical womb of schizophrenia: A review

Abstract: ABSTRACT

Cited by 18 publications

References 208 publications

Dopamine D₂ and serotonin 5‐HT_1A receptor interaction in the context of the effects of antipsychotics – in vitro studies

Dopamine D₂ and serotonin 5‐HT_1A receptor interaction in the context of the effects of antipsychotics – in vitro studies

Vitamin C in Disease Prevention and Cure: An Overview

Β-Amyloid Burden is Not Associated with Cognitive Impairment in Schizophrenia: A Systematic Review

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The biochemical womb of schizophrenia: A review

Abstract: ABSTRACT

Cited by 18 publications

References 208 publications

Dopamine D2 and serotonin 5‐HT1A receptor interaction in the context of the effects of antipsychotics – in vitro studies

Dopamine D2 and serotonin 5‐HT1A receptor interaction in the context of the effects of antipsychotics – in vitro studies

Vitamin C in Disease Prevention and Cure: An Overview

Β-Amyloid Burden is Not Associated with Cognitive Impairment in Schizophrenia: A Systematic Review

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Product

Resources

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Dopamine D₂ and serotonin 5‐HT_1A receptor interaction in the context of the effects of antipsychotics – in vitro studies

Dopamine D₂ and serotonin 5‐HT_1A receptor interaction in the context of the effects of antipsychotics – in vitro studies