Maternal alcohol exposure during mid-pregnancy dilates fetal cerebral arteries via endocannabinoid receptors

Olga Seleverstov, Ana Tobiasz, J. Scott Jackson, Ryan Sullivan, Dejian Ma, J. Pierce Sullivan, Steven Davison, Yada Akkhawattanangkul, Danielle Tate, Terry Costello, Stacey Barnett, Wei Li, Giancarlo Mari, Alejandro Dopico, Anna Bukiya

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Prenatal alcohol exposure often results in fetal alcohol syndrome and fetal alcohol spectrum disorders. Mechanisms of fetal brain damage by alcohol remain unclear. We used baboons (Papio spp.) to study alcohol-driven changes in the fetal cerebral artery endocannabinoid system. Pregnant baboons were subjected to binge alcohol exposure via gastric infusion three times during a period equivalent to the second trimester of human pregnancy. A control group was infused with orange-flavored drink that was isocaloric to the alcohol-containing solution. Cesarean sections were performed at a time equivalent to the end of the second trimester of human pregnancy. Fetal cerebral arteries were harvested and subjected to in vitro pressurization followed by pharmacological profiling. During each alcohol-infusion episode, maternal blood alcohol concentrations (BAC) reached 80 mg/dL, that is, equivalent to the BAC considered legal intoxication in humans. Circulating anandamide (AEA) and 2-arachidonoylglycerol (2-AG) remained unchanged. Ultrasound studies on pregnant mothers revealed that fetal alcohol exposure decreased peak systolic blood velocity in middle cerebral arteries when compared to pre-alcohol levels. Moreover, ethanol-induced dilation was observed in fetal cerebral arteries pressurized in vitro. This dilation was abolished by the mixture of AM251 and AM630, which block cannabinoid receptors 1 and 2, respectively. In the presence of AM251, the cannabinoid receptor agonist AEA evoked a higher, concentration-dependent dilation of cerebral arteries from alcohol-exposed fetuses. The difference in AEA-induced cerebral artery dilation vanished in the presence of AM630. CB1 and CB2 receptor mRNA and protein levels were similar in cerebral arteries from alcohol-exposed and control-exposed fetuses. In summary, alcohol exposure dilates fetal cerebral arteries via endocannabinoid receptors and results in an increased function of CB2.

Original languageEnglish (US)
Pages (from-to)51-61
Number of pages11
JournalAlcohol
Volume61
DOIs
StatePublished - Jun 1 2017

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Maternal Exposure
Endocannabinoids
Cerebral Arteries
pregnancy
alcohol
Alcohols
Pregnancy
Papio
Dilatation
Fetal Alcohol Spectrum Disorders
Second Pregnancy Trimester
Blood
Fetus
Cannabinoid Receptor CB2
Cannabinoid Receptor Agonists
Cannabinoid Receptor CB1
Cannabinoid Receptors
Middle Cerebral Artery
brain damage
Cesarean Section

All Science Journal Classification (ASJC) codes

  • Health(social science)
  • Biochemistry
  • Toxicology
  • Neurology
  • Behavioral Neuroscience

Cite this

Maternal alcohol exposure during mid-pregnancy dilates fetal cerebral arteries via endocannabinoid receptors. / Seleverstov, Olga; Tobiasz, Ana; Jackson, J. Scott; Sullivan, Ryan; Ma, Dejian; Sullivan, J. Pierce; Davison, Steven; Akkhawattanangkul, Yada; Tate, Danielle; Costello, Terry; Barnett, Stacey; Li, Wei; Mari, Giancarlo; Dopico, Alejandro; Bukiya, Anna.

In: Alcohol, Vol. 61, 01.06.2017, p. 51-61.

Research output: Contribution to journalArticle

Seleverstov, O, Tobiasz, A, Jackson, JS, Sullivan, R, Ma, D, Sullivan, JP, Davison, S, Akkhawattanangkul, Y, Tate, D, Costello, T, Barnett, S, Li, W, Mari, G, Dopico, A & Bukiya, A 2017, 'Maternal alcohol exposure during mid-pregnancy dilates fetal cerebral arteries via endocannabinoid receptors', Alcohol, vol. 61, pp. 51-61. https://doi.org/10.1016/j.alcohol.2017.01.014
Seleverstov, Olga ; Tobiasz, Ana ; Jackson, J. Scott ; Sullivan, Ryan ; Ma, Dejian ; Sullivan, J. Pierce ; Davison, Steven ; Akkhawattanangkul, Yada ; Tate, Danielle ; Costello, Terry ; Barnett, Stacey ; Li, Wei ; Mari, Giancarlo ; Dopico, Alejandro ; Bukiya, Anna. / Maternal alcohol exposure during mid-pregnancy dilates fetal cerebral arteries via endocannabinoid receptors. In: Alcohol. 2017 ; Vol. 61. pp. 51-61.
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abstract = "Prenatal alcohol exposure often results in fetal alcohol syndrome and fetal alcohol spectrum disorders. Mechanisms of fetal brain damage by alcohol remain unclear. We used baboons (Papio spp.) to study alcohol-driven changes in the fetal cerebral artery endocannabinoid system. Pregnant baboons were subjected to binge alcohol exposure via gastric infusion three times during a period equivalent to the second trimester of human pregnancy. A control group was infused with orange-flavored drink that was isocaloric to the alcohol-containing solution. Cesarean sections were performed at a time equivalent to the end of the second trimester of human pregnancy. Fetal cerebral arteries were harvested and subjected to in vitro pressurization followed by pharmacological profiling. During each alcohol-infusion episode, maternal blood alcohol concentrations (BAC) reached 80 mg/dL, that is, equivalent to the BAC considered legal intoxication in humans. Circulating anandamide (AEA) and 2-arachidonoylglycerol (2-AG) remained unchanged. Ultrasound studies on pregnant mothers revealed that fetal alcohol exposure decreased peak systolic blood velocity in middle cerebral arteries when compared to pre-alcohol levels. Moreover, ethanol-induced dilation was observed in fetal cerebral arteries pressurized in vitro. This dilation was abolished by the mixture of AM251 and AM630, which block cannabinoid receptors 1 and 2, respectively. In the presence of AM251, the cannabinoid receptor agonist AEA evoked a higher, concentration-dependent dilation of cerebral arteries from alcohol-exposed fetuses. The difference in AEA-induced cerebral artery dilation vanished in the presence of AM630. CB1 and CB2 receptor mRNA and protein levels were similar in cerebral arteries from alcohol-exposed and control-exposed fetuses. In summary, alcohol exposure dilates fetal cerebral arteries via endocannabinoid receptors and results in an increased function of CB2.",
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AU - Davison, Steven

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