The mRNA Expression Status of Dopamine Receptor D2, Dopamine Receptor D3 and DARPP-32 in T Lymphocytes of Patients with Early Psychosis

Cui, Yin; Prabhu, Vishwanath Vasudev; Nguyen, Thong Ba; Yadav, Binod Kumar; Chung, Young‐Chul

doi:10.3390/ijms161125983

Cited by 28 publications

(26 citation statements)

References 37 publications

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“…Further, DRD3 expression correlated with the excitement factor on the PANSS in patients with schizophrenia/schizophreniform disorder. According to the authors, DRD3 mRNA levels can be used as a diagnostic marker to differentiate patients with early psychosis from healthy controls [ 237 ].…”

Section: Clinical Implications Of the Effects On The Dopaminergic mentioning

confidence: 99%

Immunomodulatory Effects Mediated by Dopamine

Arreola

Álvarez-Herrera

Pérez‐Sánchez

et al. 2016

Journal of Immunology Research

108

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Dopamine (DA), a neurotransmitter in the central nervous system (CNS), has modulatory functions at the systemic level. The peripheral and central nervous systems have independent dopaminergic system (DAS) that share mechanisms and molecular machinery. In the past century, experimental evidence has accumulated on the proteins knowledge that is involved in the synthesis, reuptake, and transportation of DA in leukocytes and the differential expression of the D1-like (D1R and D5R) and D2-like receptors (D2R, D3R, and D4R). The expression of these components depends on the state of cellular activation and the concentration and time of exposure to DA. Receptors that are expressed in leukocytes are linked to signaling pathways that are mediated by changes in cAMP concentration, which in turn triggers changes in phenotype and cellular function. According to the leukocyte lineage, the effects of DA are associated with such processes as respiratory burst, cytokine and antibody secretion, chemotaxis, apoptosis, and cytotoxicity. In clinical conditions such as schizophrenia, Parkinson disease, Tourette syndrome, and multiple sclerosis (MS), there are evident alterations during immune responses in leukocytes, in which changes in DA receptor density have been observed. Several groups have proposed that these findings are useful in establishing clinical status and clinical markers.

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Section: Clinical Implications Of the Effects On The Dopaminergic mentioning

confidence: 99%

Immunomodulatory Effects Mediated by Dopamine

Arreola

Álvarez-Herrera

Pérez‐Sánchez

et al. 2016

Journal of Immunology Research

108

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“…Unfortunately, there are on this topic inconclusive reports as well. No change in DARPP-32 protein levels were found in schizophrenic prefrontal and cingulate cortex and T lymphocytes of elderly patients with schizophrenia [ 75 , 76 ]. Mutation analysis of DARPP-32 gene indicate that it is not a major susceptibility gene for schizophrenia [ 77 ].…”

Section: Introductionmentioning

confidence: 99%

The involvement of DARPP-32 in the pathophysiology of schizophrenia

et al. 2017

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Schizophrenia is one of the most devastating heterogeneous psychiatric disorders. The dopamine hypothesis is the longest standing pathoetiologic theory of schizophrenia based on neurochemical evidences of elevated brain striatal dopamine synthesis capacity and increased dopamine release in response to stress. Dopamine and cyclic AMP-regulated phosphoprotein of relative molecular mass 32,000 (DARPP-32) is a cytosolic protein highly enriched in the medium spiny neurons of the neostriatum, considered as the most important integrator between the cortical input and the basal ganglia, and associated with motor control. Accumulating evidences has indicated the involvement of DARPP-32 in the development of schizophrenia; i. DARPP-32 phosphorylation is regulated by several neurotransmitters, including dopamine and glutamate, neurotransmitters implicated in schizophrenia pathogenesis; ii. decrease of both total and phosphorylated DARPP-32 in the prefrontal cortex are observed in schizophrenic animal models; iii. postmortem brain studies indicated decreased expression of DARPP-32 protein in the superior temporal gyrus and dorsolateral prefrontal cortex in patients with schizophrenia; iv. DARPP-32 phosphorylation is increased upon therapy with antipsychotic drugs, such as haloperidol and risperidone which improve behavioral performance in experimental animal models and patients; v. Genetic analysis of the gene coding for DARPP-32 propose an association with schizophrenia. Cumulatively, these findings implicate DARPP-32 protein in schizophrenia and propose it as a potential therapeutic target. Here, we summarize the possible roles of DARPP-32 during the development of schizophrenia and make some recommendations for future research. We propose that DARPP-32 and its interacting proteins may serve as potential therapeutic targets in the treatment of schizophrenia.

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“…Regarding rs6280 polymorphism alone, a recent study demonstrated that levels of DRD3 mRNA on T lymphocytes were significantly different between controls and individuals with unspecified psychotic disorder and SCZ (Cui et al, 2015). Another study showed that there is an excess of the C allele and homozygotes for this allele in patients with tardive dyskinesia (an irreversible adverse effect of the antipsychotic medication) (Utsunomiya et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…To try to understand the refractoriness of several drugs a pharmacogenetic approach has been used. Pharmacogenetics place genetic variation as a possible reason for the absence or poor response to adequate medication (Cui et al, 2015). Large-scale genomic association studies of SCZ identified 108 genetic loci associated with this disorder.…”

Section: Introductionmentioning

confidence: 99%

Research Article Frequency of ANKK1, DRD2, DRD3 gene polymorphisms in refractory schizophrenia patients

Nunes¹,

Pinto²,

Freitas³

et al. 2019

Genet. Mol. Res.

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Schizophrenia is considered one of the most severe and complex mental disorders; it affects both the quality of life of the patient and his family. The dopamine hypothesis is the main concept concerning antipsychotic activity. Patients with treatment-refractory schizophrenia have a lower capacity for dopamine synthesis than those with a good response to first-generation antipsychotics. The polymorphisms rs1800497, rs1799732 and rs6280were chosen for evaluation because they are associated with decreased dopamine receptor expression and occur in genes encoding these receptors, namely, ANKK1, DRD2 and DRD3, respectively. This effect caused by these polymorphisms enhances refractoriness to treatment. We investigated the frequency of these polymorphisms and evaluated their association with refractory schizophrenia. This was a casecontrol molecular genetic study, with patients who were divided into three groups of 72 participants each: patients with refractory schizophrenia, with schizophrenia and controls with no diagnosis of any type of mental disorder. All participants of the research were from the extended Midwest region of Minas Gerais. Polymorphisms were evaluated by PCR followed by RFLP. The allele and genotype ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 18 (4): gmr18389 F.D.D. Nunes et al. 2 frequencies were determined, the association tests performed using Pearson's Chi Square, and Odds Ratio values were estimated. Genotypic models of dominance and heterosis were constructed. An association of the Del C allele of rs1799732 polymorphism and schizophrenia (P = 0.03) was found. Further research on this subject is merited, since response to treatment is of utmost importance to the patient's quality of life.

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The mRNA Expression Status of Dopamine Receptor D2, Dopamine Receptor D3 and DARPP-32 in T Lymphocytes of Patients with Early Psychosis

Cited by 28 publications

References 37 publications

Immunomodulatory Effects Mediated by Dopamine

Immunomodulatory Effects Mediated by Dopamine

The involvement of DARPP-32 in the pathophysiology of schizophrenia

Research Article Frequency of <i>ANKK1</i>, <i>DRD2</i>, <i>DRD3</i> gene polymorphisms in refractory schizophrenia patients

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