Stress changes amphetamine response, D2 receptor expression and epigenetic regulation in low-anxiety rats

Kołosowska, Karolina; Gawryluk, Aleksandra; Wisłowska-Stanek, Aleksandra; Liguz-Lecznar, Monika; Hetmańczyk, Katarzyna; Ługowska, Agnieszka; Sobolewska, Alicja; Skórzewska, Anna; Gryz, Marek; Lehner, Małgorzata

doi:10.1016/j.pnpbp.2019.04.009

Cited by 10 publications

(11 citation statements)

References 115 publications

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“…Given that enhanced mesocorticolimbic dopamine response [ 16 ] and increased phasic activity of ventral tegmental area dopamine neurons [ 18 ] were reported in animals exposed to SDS, this finding seems to reflect a compensatory response to the overstimulation of D2L caused by increased dopamine release. On the other hand, the finding of increased expression of D2L in the AMY of the SUS group compared to the CON group conflicts with previous studies variously reporting decreased [ 52 , 53 ] and increased [ 54 ] expression of Drd2 in the AMY of defeated mice. Nevertheless, considering the role of AMY in vigilance and danger detection, and its higher concentration of Drd2 [ 55 ], this result may reflect vulnerability in SUS mice.…”

Section: Discussioncontrasting

confidence: 93%

Risperidone Induced DNA Methylation Changes in Dopamine Receptor and Stathmin Genes in Mice Exposed to Social Defeat Stress

Rami

Nguyen

et al. 2022

Clin Psychopharmacol Neurosci

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Objective Understanding complex epigenetic mechanisms is necessary to fully elucidate the effects of antipsychotic drug. This study investigated DNA methylation and mRNA expression levels of dopamine D2 and D1 receptor (Drd2 and Drd1, respectively), nuclear receptor subfamily 3, group C, member 1 (Nr3c1) and stathmin 1 (Stmn1) in brain regions of mice exposed to social defeat stress (SDS) and effects of risperidone on altered methylation and mRNA expression levels induced by SDS. Methods Following SDS for 10 days, risperidone (0.2 mg/kg) or vehicle was administered to adult mice for 7 days. Brain tissues from the prefrontal cortex (PFC), hippocampus (HIP) and amygdala (AMY) were processed to measure methylation and mRNA levels of Drd2, Drd1, Nr3c1 and Stmn1 using pyrosequencing and real time-polymerase chain reaction. Results We found altered methylation status of Nr3c1 and Stmn1 in the HIP and AMY of mice exposed to SDS. These changes were reversed by risperidone treatment. In addition, different methylation patterns of Drd2 and Drd1 in the PFC and AMY between defeated and control mice were identified with risperidone treatment. Conclusion These findings suggest that risperidone can cause epigenetic changes in Drd2, Drd1, Nr3c1 and Stmn1 in defeated mice. These changes could be epigenetic mechanisms underlying antipsychotic efficacy.

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Section: Discussioncontrasting

confidence: 93%

Risperidone Induced DNA Methylation Changes in Dopamine Receptor and Stathmin Genes in Mice Exposed to Social Defeat Stress

Rami

Nguyen

et al. 2022

Clin Psychopharmacol Neurosci

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“…Yet another study used Bioinformatic analysis to identify putative gene targets for these stress-responsive microRNAs, some of which were known to be associated with stress. One of the prominent stress-induced microRNAs found in this screen, miR-34c, was further confirmed to be upregulated after acute and chronic stressful challenge and downregulated in Dicer ablated cells [17,18]. Based upon these studies, we can assume that miRNAs probably serve a significant role in gene modulation and regulation in psychiatric diseases.…”

Section: Roc Curve Of Mir-26b Expression For Sz Patient and Mdd Patient Differentiationsupporting

confidence: 62%

Diagnostic Value of miR-26b in Schizophrenia

Kong¹,

Zhu²,

Zhang³

2021

Int J Blood Res Disord

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Objectives: This study aimed to investigate the diagnostic value of peripheral microRNA (miRNA) expression in schizophrenia (SZ). Methods: By using an Affymetrix array to identify differentially expressed miRNAs in SZ patients; quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to verify identified microRNA and test major depressive disorder (MDD), generalized anxiety disorder (GAD) and mental retardation (MD) related microRNAs for comparison. Results:The expression levels of miR-1972, miR-26b, miR-4485, miR-4498 and miR-4743 were up-regulated significantly in MDD patients, among which the expression levels of miR-26b, miR-4485 and miR-4743 were also upregulated significantly in GAD patients, and miR-4485 and miR-4743 upregulated in MD patients; The ROC curve of miR-26b in SZ patients showed that its sensitivity and specificity for diagnosis were 0.721 and 0.950 respectively with the area under curve (AUC) being 0.868; the ROC of miR-26b for SZ and MD differentiation showed that its sensitivity and specificity were 0.78 and 0.65 respectively with AUC being 0.765; the ROC of miR-26b for SZ and GAD differentiation showed that its sensitivity and specificity were 0.667 and 0.825 respectively with AUC being 0.802; the ROC of miR-26b for SZ and MDD differentiation showed that its sensitivity and specificity were 0.537 and 0.675 respectively with AUC being 0.629. Conclusions:MiR-26b might have significant diagnostic value for SZ, and probably also serve a significant role in MDD.

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“…The quality of the total RNA was further verified using the Agilent 2100 Bioanalyzer (Agilent RNA 6000 Pico Kit; Agilent Technologies). The analysis of mRNA and miRNA was performed according to the previously described method [34]. Realtime PCR analysis was done using PikoReal™ Real-Time PCR System (Thermo Fisher Scientific) with PowerSYBR ® Green PCR Master Mix (Applied Biosystems), specific primers for D2R gene (5′ → 3′, F:CAA CAA TAC AGA CCA GAA TGAG; R:CAG CAG AGT GAC GAT GAA ), and cDNA (concentration 5 ng/μl) for each sample in the total volume of 10 μl.…”

Section: Real-time Pcrmentioning

confidence: 99%

The effects of the recurrent social isolation stress on fear extinction and dopamine D2 receptors in the amygdala and the hippocampus

et al. 2022

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Background The present study assessed the influence of recurrent social isolation stress on the aversive memory extinction and dopamine D2 receptors (D2R) expression in the amygdala and the hippocampus subnuclei. We also analyzed the expression of epigenetic factors potentially associated with fear extinction: miRNA-128 and miRNA-142 in the amygdala. Methods Male adult fear-conditioned rats had three episodes of 48 h social isolation stress before each fear extinction session in weeks intervals. Ninety minutes after the last extinction session, the D2R expression in the nuclei of the amygdala and the hippocampus (immunocytochemical technique), and mRNA levels for D2R in the amygdala were assessed (PCR). Moreover, we evaluated the levels of miRNA-128 and miRNA-142 in the amygdala. Results It was found that recurrent social isolation stress decreased the fear extinction rate. The extinguished isolated rats were characterized by higher expression of D2R in the CA1 area of the hippocampus compared to the extinguished and the control rats. In turn, the isolated group presented higher D2R immunoreactivity in the CA1 area compared to the extinguished, the control, and the extinguished isolated animals. Moreover, the extinguished animals had higher expression of D2R in the central amygdala than the control and the extinguished isolated rats. These changes were accompanied by the increase in miRNA-128 level in the amygdala in the extinguished isolated rats compared to the control, the extinguished, and the isolated rats. Moreover, the extinguished rats had lower expression of miRNA-128 compared to the control and the isolated animals. Conclusions Our results suggest that social isolation stress impairs aversive memory extinction and coexists with changes in the D2R expression in the amygdala and hippocampus and increased expression of miRNA-128 in the amygdala.

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Stress changes amphetamine response, D2 receptor expression and epigenetic regulation in low-anxiety rats

Cited by 10 publications

References 115 publications

Risperidone Induced DNA Methylation Changes in Dopamine Receptor and Stathmin Genes in Mice Exposed to Social Defeat Stress

Risperidone Induced DNA Methylation Changes in Dopamine Receptor and Stathmin Genes in Mice Exposed to Social Defeat Stress

Diagnostic Value of miR-26b in Schizophrenia

The effects of the recurrent social isolation stress on fear extinction and dopamine D2 receptors in the amygdala and the hippocampus

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