Neuroprotective peptides influence cytokine and chemokine alterations in a model of fetal alcohol syndrome

Robin Roberson, Thea Kuddo, Ines Benassou, Daniel Abebe, Catherine Y. Spong

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objective: Fetal alcohol syndrome (FAS) is associated with intellectual disability and neurodevelopmental abnormalities. Neuroprotective peptides NAPVSIPQ (NAP) and SALLRSIPA (SAL) can prevent some of the alcohol-induced teratogenesis including fetal death, growth abnormalities, and learning impairment in part by preventing alcohol-induced alterations in N-methyl-D-aspartate receptor gene expression in a mouse model for FAS. We evaluated a panel of cytokines and chemokines to determine whether NAP plus SAL work through a cytokine/chemokine-mediated pathway in preventing these alterations. Study Design: Using a well-characterized FAS model, timed, pregnant C57BL6/J mice were treated on gestational day (E) 8 with alcohol (0.03 mL/g), placebo, or alcohol plus peptides. Embryos were evaluated at 2 time points: after 6 hours and 10 days later at E18. A panel of cytokines/chemokines was measured using a microsphere-based multiplex immunoassay (Luminex xMAP; Millipore, Billerica, MA). Statistical analysis included Kruskal-Wallis, with P <.05 considered significant. Results: Six hours after treatment, interleukin (IL)-6 and keratinocyte chemoattractant cytokine (KC) were not detectable in the control embryos. Alcohol treatment resulted in detectable levels and significant increases in IL-6 (median, 15.7; range, 10.1-45.9 pg/mL) and KC (median, 45.9; range, 32.5-99.1 pg/mL). Embryos exposed to alcohol plus NAP plus SAL had undetectable IL-6 and KC (both P <.003), similar to the controls. Alcohol exposure resulted in a significant increase of granulocyte colony-stimulating factor (G-CSF) (P <.003) as compared with controls, and treatment with NAP plus SAL prevented the alcohol-induced increase. IL-13 and IL-1β were decreased 6 hours after alcohol exposure, and exposure to alcohol plus NAP plus SAL did not completely ameliorate the decrease. At E18, 10 days after exposure, these alterations were no longer present. Several analytes (regulated upon activation, normal T cell expressed, and secreted, tumor necrosis factor-α, interferon-γ, and IL-4) were not detectable at either time point in any of the groups. Conclusion: Prenatal alcohol exposure acutely results in a significant elevation of IL-6, G-CSF and the KC, which are known to affect N-methyl-D-aspartate receptors. NAP plus SAL treatment prevented alcohol-induced increases. This provides additional insight into the mechanism of alcohol damage in FAS and NAP plus SAL prevention of neurodevelopmental anomalies.

Original languageEnglish (US)
Pages (from-to)499.e1-499.e5
JournalAmerican journal of obstetrics and gynecology
Volume207
Issue number6
DOIs
StatePublished - Dec 2012
Externally publishedYes

Fingerprint

Fetal Alcohol Spectrum Disorders
Chemokines
Alcohols
Cytokines
Peptides
Chemotactic Factors
Keratinocytes
Interleukin-6
Embryonic Structures
Granulocyte Colony-Stimulating Factor
N-Methyl-D-Aspartate Receptors
Teratogenesis
Fetal Death
Interleukin-13
Fetal Development
SALLRSIPA
Interleukin-1
Microspheres
Immunoassay
Intellectual Disability

Keywords

  • fetal alcohol syndrome
  • fetal death
  • growth abnormalities
  • learning impairment
  • NAPVSIPQ
  • neurodevelopmental abnormalities
  • SALLRSIPA

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Neuroprotective peptides influence cytokine and chemokine alterations in a model of fetal alcohol syndrome. / Roberson, Robin; Kuddo, Thea; Benassou, Ines; Abebe, Daniel; Spong, Catherine Y.

In: American journal of obstetrics and gynecology, Vol. 207, No. 6, 12.2012, p. 499.e1-499.e5.

Research output: Contribution to journalArticle

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T1 - Neuroprotective peptides influence cytokine and chemokine alterations in a model of fetal alcohol syndrome

AU - Roberson, Robin

AU - Kuddo, Thea

AU - Benassou, Ines

AU - Abebe, Daniel

AU - Spong, Catherine Y.

PY - 2012/12

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N2 - Objective: Fetal alcohol syndrome (FAS) is associated with intellectual disability and neurodevelopmental abnormalities. Neuroprotective peptides NAPVSIPQ (NAP) and SALLRSIPA (SAL) can prevent some of the alcohol-induced teratogenesis including fetal death, growth abnormalities, and learning impairment in part by preventing alcohol-induced alterations in N-methyl-D-aspartate receptor gene expression in a mouse model for FAS. We evaluated a panel of cytokines and chemokines to determine whether NAP plus SAL work through a cytokine/chemokine-mediated pathway in preventing these alterations. Study Design: Using a well-characterized FAS model, timed, pregnant C57BL6/J mice were treated on gestational day (E) 8 with alcohol (0.03 mL/g), placebo, or alcohol plus peptides. Embryos were evaluated at 2 time points: after 6 hours and 10 days later at E18. A panel of cytokines/chemokines was measured using a microsphere-based multiplex immunoassay (Luminex xMAP; Millipore, Billerica, MA). Statistical analysis included Kruskal-Wallis, with P <.05 considered significant. Results: Six hours after treatment, interleukin (IL)-6 and keratinocyte chemoattractant cytokine (KC) were not detectable in the control embryos. Alcohol treatment resulted in detectable levels and significant increases in IL-6 (median, 15.7; range, 10.1-45.9 pg/mL) and KC (median, 45.9; range, 32.5-99.1 pg/mL). Embryos exposed to alcohol plus NAP plus SAL had undetectable IL-6 and KC (both P <.003), similar to the controls. Alcohol exposure resulted in a significant increase of granulocyte colony-stimulating factor (G-CSF) (P <.003) as compared with controls, and treatment with NAP plus SAL prevented the alcohol-induced increase. IL-13 and IL-1β were decreased 6 hours after alcohol exposure, and exposure to alcohol plus NAP plus SAL did not completely ameliorate the decrease. At E18, 10 days after exposure, these alterations were no longer present. Several analytes (regulated upon activation, normal T cell expressed, and secreted, tumor necrosis factor-α, interferon-γ, and IL-4) were not detectable at either time point in any of the groups. Conclusion: Prenatal alcohol exposure acutely results in a significant elevation of IL-6, G-CSF and the KC, which are known to affect N-methyl-D-aspartate receptors. NAP plus SAL treatment prevented alcohol-induced increases. This provides additional insight into the mechanism of alcohol damage in FAS and NAP plus SAL prevention of neurodevelopmental anomalies.

AB - Objective: Fetal alcohol syndrome (FAS) is associated with intellectual disability and neurodevelopmental abnormalities. Neuroprotective peptides NAPVSIPQ (NAP) and SALLRSIPA (SAL) can prevent some of the alcohol-induced teratogenesis including fetal death, growth abnormalities, and learning impairment in part by preventing alcohol-induced alterations in N-methyl-D-aspartate receptor gene expression in a mouse model for FAS. We evaluated a panel of cytokines and chemokines to determine whether NAP plus SAL work through a cytokine/chemokine-mediated pathway in preventing these alterations. Study Design: Using a well-characterized FAS model, timed, pregnant C57BL6/J mice were treated on gestational day (E) 8 with alcohol (0.03 mL/g), placebo, or alcohol plus peptides. Embryos were evaluated at 2 time points: after 6 hours and 10 days later at E18. A panel of cytokines/chemokines was measured using a microsphere-based multiplex immunoassay (Luminex xMAP; Millipore, Billerica, MA). Statistical analysis included Kruskal-Wallis, with P <.05 considered significant. Results: Six hours after treatment, interleukin (IL)-6 and keratinocyte chemoattractant cytokine (KC) were not detectable in the control embryos. Alcohol treatment resulted in detectable levels and significant increases in IL-6 (median, 15.7; range, 10.1-45.9 pg/mL) and KC (median, 45.9; range, 32.5-99.1 pg/mL). Embryos exposed to alcohol plus NAP plus SAL had undetectable IL-6 and KC (both P <.003), similar to the controls. Alcohol exposure resulted in a significant increase of granulocyte colony-stimulating factor (G-CSF) (P <.003) as compared with controls, and treatment with NAP plus SAL prevented the alcohol-induced increase. IL-13 and IL-1β were decreased 6 hours after alcohol exposure, and exposure to alcohol plus NAP plus SAL did not completely ameliorate the decrease. At E18, 10 days after exposure, these alterations were no longer present. Several analytes (regulated upon activation, normal T cell expressed, and secreted, tumor necrosis factor-α, interferon-γ, and IL-4) were not detectable at either time point in any of the groups. Conclusion: Prenatal alcohol exposure acutely results in a significant elevation of IL-6, G-CSF and the KC, which are known to affect N-methyl-D-aspartate receptors. NAP plus SAL treatment prevented alcohol-induced increases. This provides additional insight into the mechanism of alcohol damage in FAS and NAP plus SAL prevention of neurodevelopmental anomalies.

KW - fetal alcohol syndrome

KW - fetal death

KW - growth abnormalities

KW - learning impairment

KW - NAPVSIPQ

KW - neurodevelopmental abnormalities

KW - SALLRSIPA

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