Your browser doesn't support javascript.
loading
Sex-specific inflammatory and white matter effects of prenatal opioid exposure: a pilot study.
Yen, Elizabeth; Madan, Neel; Tarui, Tomo; Kaneko-Tarui, Tomoko; Breeze, Janis L; Davis, Jonathan M; Maron, Jill L.
Afiliação
  • Yen E; Mother Infant Research Institute (MIRI), Tufts Medical Center, Boston, MA, USA. eyen@tuftsmedicalcenter.org.
  • Madan N; Department of Pediatrics, Tufts Medical Center, Boston, MA, USA. eyen@tuftsmedicalcenter.org.
  • Tarui T; Department of Radiology, Tufts Medical Center, Boston, MA, USA.
  • Kaneko-Tarui T; Mother Infant Research Institute (MIRI), Tufts Medical Center, Boston, MA, USA.
  • Breeze JL; Department of Pediatrics, Tufts Medical Center, Boston, MA, USA.
  • Davis JM; Mother Infant Research Institute (MIRI), Tufts Medical Center, Boston, MA, USA.
  • Maron JL; Tufts Clinical and Translational Science Institute, Tufts University, Boston, MA, USA.
Pediatr Res ; 93(3): 604-611, 2023 02.
Article em En | MEDLINE | ID: mdl-36280708
ABSTRACT

BACKGROUND:

Preclinical data demonstrate that opioids modulate brain reward signaling through an inflammatory cascade, but this relationship has yet to be studied in opioid-exposed neonates.

METHODS:

Saliva samples of 54 opioid-exposed and sex- and age-matched non-exposed neonates underwent transcriptomic analysis of inflammatory and reward genes. A subset of 22 neonates underwent brain magnetic resonance imaging (MRI) to evaluate white matter injury commonly associated with inflammatory response. Gene expression and brain MRI were compared between opioid- and non-exposed neonates and further stratified by sex and pharmacotherapy need.

RESULTS:

Opioid-exposed females regardless of pharmacotherapy need had higher expression of inflammatory genes than their male counterparts, with notable differences in the expression of CCL2 and CXCL1 in females requiring pharmacotherapy (p = 0.01 and 0.06, respectively). Opioid-exposed males requiring pharmacotherapy had higher expression of DRD2 than exposed females (p = 0.07), validating our prior research. Higher expression of IL1ß, IL6, TNFα, and IL10 was seen in opioid-exposed neonates with T1 white matter hyperintensity (WMH) compared to exposed neonates without WMH (p < 0.05).

CONCLUSION:

Prenatal opioid exposure may promote inflammation resulting in changes in reward signaling and white matter injury in the developing brain, with unique sex-specific effects. The actions of opioids through non-neuronal pathways need further investigation. IMPACT Opioid-exposed neonates are at risk for punctate T1 white matter hyperintensity (WMH). Females carry a greater propensity for WMH. Salivary transcriptomic data showed significantly higher expression of inflammatory genes in opioid-exposed neonates with WMH than those without WMH, irrespective of pharmacotherapy need. Adding to prior studies, our findings suggest that prenatal opioid exposure may modulate white matter injury and reward signaling through a pro-inflammatory process that is sex specific. This novel study highlights the short-term molecular and structural effects of prenatal opioids and the need to elucidate the long-term impact of prenatal opioid exposure.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Lesões Encefálicas / Substância Branca Limite: Female / Humans / Male / Newborn / Pregnancy Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Lesões Encefálicas / Substância Branca Limite: Female / Humans / Male / Newborn / Pregnancy Idioma: En Ano de publicação: 2023 Tipo de documento: Article