Effects of prenatal opioid and alcohol exposures on immune and serotonin factors in human placenta

Ruyak, Sharon L.; Noor, Shahani; DiDomenico, Jared; Sun, Melody S.; Oropeza, Annette K. Fernandez; Rodriguez, Dominique E.; Marquez, Lidia Enriquez; Milligan, Erin D.; Bakhireva, Ludmila N.

doi:10.1016/j.expneurol.2022.114057

Cited by 9 publications

(3 citation statements)

References 99 publications

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“…Several preclinical studies reported heightened brain proinflammatory cytokines due to PAE (Drew et al, 2015;Terasaki and Schwarz, 2016;Pascual et al, 2017). Both animal and clinical studies show that the underlying biological vulnerability due to PAE that extends to chronic CNS disease is driven by dysfunctional CNS-immune interactions (Drew and Kane, 2014;Wilhelm and Guizzetti, 2015;Terasaki and Schwarz, 2017;Bodnar et al, 2018Bodnar et al, , 2020Ruyak et al, 2022). Little is known about how PAE-related changes lead to chronic CNS dysfunction triggered by challenges in adulthood.…”

Section: Introductionmentioning

confidence: 99%

Prenatal alcohol exposure dysregulates spinal and circulating immune cell circular RNA expression in adult female rats with chronic sciatic neuropathy

Noor,

Pritha,

Pasmay

et al. 2023

Front. Neurosci.

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Alcohol consumption during pregnancy is associated with Fetal Alcohol Spectrum Disorders (FASD) that results in a continuum of central nervous system (CNS) deficits. Emerging evidence from both preclinical and clinical studies indicate that the biological vulnerability to chronic CNS disease in FASD populations is driven by aberrant neuroimmune actions. Our prior studies suggest that, following minor nerve injury, prenatal alcohol exposure (PAE) is a risk factor for developing adult-onset chronic pathological touch sensitivity or allodynia. Allodynia in PAE rats occurs concurrently with heightened proinflammatory peripheral and spinal glial-immune activation. However, minor nerve-injured control rats remain non-allodynic, and corresponding proinflammatory factors are unaltered. A comprehensive molecular understanding of the mechanism(s) that underlie PAE-induced proinflammatory bias during adulthood remains elusive. Non-coding circular RNAs (circRNAs) are emerging as novel modulators of gene expression. Here, we hypothesized that PAE induces dysregulation of circRNAs that are linked to immune function under basal and nerve-injured conditions during adulthood. Utilizing a microarray platform, we carried out the first systematic profiling of circRNAs in adult PAE rats, prior to and after minor nerve injury. The results demonstrate a unique circRNA profile in adult PAE rats without injury; 18 circRNAs in blood and 32 spinal circRNAs were differentially regulated. Following minor nerve injury, more than 100 differentially regulated spinal circRNAs were observed in allodynic PAE rats. Bioinformatic analysis identified that the parental genes of these circRNAs are linked to the NF-κB complex, a central transcription factor for pain-relevant proinflammatory cytokines. Quantitative real-time PCR was employed to measure levels of selected circRNAs and linear mRNA isoforms. We have validated that circVopp1 was significantly downregulated in blood leukocytes in PAE rats, concurrent with downregulation of Vopp1 mRNA levels. Spinal circVopp1 levels were upregulated in PAE rats, regardless of nerve injury. Additionally, PAE downregulated levels of circItch and circRps6ka3, which are linked to immune regulation. These results demonstrate that PAE exerts long-lasting dysregulation of circRNA expression in blood leukocytes and the spinal cord. Moreover, the spinal circRNA expression profile following peripheral nerve injury is differentially modulated by PAE, potentially contributing to PAE-induced neuroimmune dysregulation.

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Section: Introductionmentioning

confidence: 99%

Prenatal alcohol exposure dysregulates spinal and circulating immune cell circular RNA expression in adult female rats with chronic sciatic neuropathy

Noor,

Pritha,

Pasmay

et al. 2023

Front. Neurosci.

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“…As with PE, downregulation of MAOA expression in the placenta has been associated with increased symptoms of maternal depression during pregnancy ( 130 ). Maternal alcohol consumption during pregnancy was associated with decreased SERT mRNA levels and increased TPH1 mRNA levels in the placenta ( 131 ).…”

Section: Serotonin System and Its Components In The Human Placentamentioning

confidence: 99%

Serotonin system in the human placenta – the knowns and unknowns

et al. 2022

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The biogenic monoamine serotonin (5-hydroxytryptamine, 5-HT) is a chemical messenger widely distributed in the brain and various other organs. Its homeostasis is maintained by the coordinated activity of a variety of proteins, including enzymes of serotonin metabolism, transmembrane transporters of serotonin, and serotonin receptors. The serotonin system has been identified also in the placenta in rodent models as a key component of placental physiology. However, serotonin pathways in the human placenta are far from well understood. Their alterations may have long-lasting consequences for the fetus that can manifest later in life. In this review, we summarize information on the location of the components of the serotonin system in the human placenta, their regulation, function, and alterations in pathological pregnancies. We highlight current controversies and discuss important topics for future research.

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“…Though complete abstinence is recommended, prenatal alcohol exposure remains common, especially before recognition of pregnancy. Moreover, opioid use impairs fetal neurodevelopment and general health by disturbing the dynamic interaction along the maternal–placental–fetal axis 4 . Missing information about in‐utero exposure to alcohol and medication could have biased the conclusions and should be supplemented.…”

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confidence: 99%

Neurosonographic evaluation of corpus callosum–fastigium and tectal length in late‐onset small fetuses

Tan,

Wang,

et al. 2024

Ultrasound in Obstet & Gyne

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Effects of prenatal opioid and alcohol exposures on immune and serotonin factors in human placenta

Cited by 9 publications

References 99 publications

Prenatal alcohol exposure dysregulates spinal and circulating immune cell circular RNA expression in adult female rats with chronic sciatic neuropathy

Prenatal alcohol exposure dysregulates spinal and circulating immune cell circular RNA expression in adult female rats with chronic sciatic neuropathy

Serotonin system in the human placenta – the knowns and unknowns

Neurosonographic evaluation of corpus callosum–fastigium and tectal length in late‐onset small fetuses

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