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Expression of Dopamine D_1-4 and Serotonin 5-HT_1A-3A Receptors in Blood Mononuclear Cells in Schizophrenia.

ABSTRACT: Introduction: The aim of this study was to determine the mRNA expression profile of dopamine D₁, D₂, D₃, D₄ and serotonin 5-HT_1A, 5-HT_2A, and 5-HT_3A receptors in peripheral blood mononuclear cells (PBMCs) in schizophrenia and the in vitro effect of antipsychotics on the expression of these receptors in PBMCs of healthy subjects. Materials and Methods: Twenty-seven patients with schizophrenia and 29 healthy controls were recruited for the study. All study subjects underwent thorough clinical assessment, including anthropometric and body composition measurements. The expression of mRNA for dopamine D_1-4 and serotonin 5-HT_1A-3A receptors was measured using quantitative RT-PCR in peripheral blood mononuclear cells. In vitro mRNA and protein expression of these receptors was measured using quantitative RT-PCR and Western Blotting in PBMCs cultured with quetiapine, haloperidol, aripiprazole, risperidone, olanzapine or clozapine at IC₅₀, half of IC₅₀, and one-quarter of IC₅₀ concentrations. Results: The key finding was that the schizophrenia group demonstrated significantly higher mRNA expression of D₁, D₂ and D₄ receptors (p < 0.001), and significantly lower mRNA expression of 5-HT_3A receptors (p < 0.01). After adjusting for smoking, the mRNA expression of D₁ lost its significance, while that of D₃, 5-HT_1A, 5-HT_2A became significant (all three were lower in the schizophrenia group). These receptors also demonstrated different ratios of mRNA expression in the schizophrenia group. The in vitro experiments showed that high concentrations of antipsychotics influenced the mRNA and protein expression of all studied receptors. Conclusion: Schizophrenia patients display a distinctive pattern of dopamine and serotonin receptor mRNA expression in blood mononuclear cells. This expression is little affected by antipsychotic treatment and it may therefore serve as a useful diagnostic biomarker for schizophrenia.

SUBMITTER: Wysokinski A

PROVIDER: S-EPMC7988204 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Serotoninergic (5-HT) neurons are powerful modulators of spinal locomotor circuits. Most studies on 5-HT modulation focused on the effect of exogenous 5-HT and these studies provided key information about the cellular mechanisms involved. Less is known about the effects of increased release of endogenous 5-HT with selective serotonin reuptake inhibitors. In mammals, such molecules were shown to destabilize the fictive locomotor output of spinal limb networks through 5-HT1A receptors. However, in tetrapods little is known about the effects of increased 5-HT release on the locomotor output of axial networks, which are coordinated with limb circuits during locomotion from basal vertebrates to mammals. Here, we examined the effect of citalopram on fictive locomotion generated in axial segments of isolated spinal cords in salamanders, a tetrapod where raphe 5-HT reticulospinal neurons and intraspinal 5-HT neurons are present as in other vertebrates. Using electrophysiological recordings of ventral roots, we show that fictive locomotion generated by bath-applied glutamatergic agonists is destabilized by citalopram. Citalopram-induced destabilization was prevented by a 5-HT1A receptor antagonist, whereas a 5-HT1A receptor agonist destabilized fictive locomotion. Using immunofluorescence experiments, we found 5-HT-positive fibers and varicosities in proximity with motoneurons and glutamatergic interneurons that are likely involved in rhythmogenesis. Our results show that increasing 5-HT release has a deleterious effect on axial locomotor activity through 5-HT1A receptors. This is consistent with studies in limb networks of turtle and mouse, suggesting that this part of the complex 5-HT modulation of spinal locomotor circuits is common to limb and axial networks in limbed vertebrates.NEW & NOTEWORTHY Little is known about the modulation exerted by endogenous serotonin on axial locomotor circuits in tetrapods. Using axial ventral root recordings in salamanders, we found that a serotonin reuptake blocker destabilized fictive locomotor activity through 5-HT1A receptors. Our anatomical results suggest that serotonin is released on motoneurons and glutamatergic interneurons possibly involved in rhythmogenesis. Our study suggests that common serotoninergic mechanisms modulate axial motor circuits in amphibians and limb motor circuits in reptiles and mammals.

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Expression of Dopamine D_1-4 and Serotonin 5-HT_1A-3A Receptors in Blood Mononuclear Cells in Schizophrenia.

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Dataset Information

Expression of Dopamine D1-4 and Serotonin 5-HT1A-3A Receptors in Blood Mononuclear Cells in Schizophrenia.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Expression of Dopamine D_1-4 and Serotonin 5-HT_1A-3A Receptors in Blood Mononuclear Cells in Schizophrenia.