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Diverse changes in myelin protein expression in rat brain after perinatal methadone exposure
Rahul Oberoi1, Tianci Chu2, Nicholas Mellen3
1Division of Neonatology, Department of Pediatrics, University of Louisville School of Medicine, Louisville, USA.
Insights
Antenatal opioid exposure, specifically methadone, significantly impacts neonatal rat brain development. This study reveals regionally-specific alterations in brain myelination and myelin proteins in exposed pups.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Neonatal Abstinence Syndrome (NAS) incidence has risen due to increased antenatal opioid exposure.
- Opioid exposure during gestation affects the developing brain.
- Methadone is a common treatment for opioid use disorder during pregnancy.
Purpose of the Study:
- To investigate the effects of perinatal methadone exposure on brain myelination in developing rats.
- To analyze specific myelin proteins in different brain regions.
Main Methods:
- Pregnant Sprague-Dawley rats were exposed to methadone during gestation and/or lactation.
- Neonatal rat brains (cerebral cortex, hippocampus, cerebellum, brainstem) were analyzed for myelin proteins (CNP, PLP, MBP) using Western blot.
- Exposure durations included through postnatal day 7 and day 19.
Main Results:
- Methadone exposure decreased CNP, PLP, and MBP expression in the cerebral cortex and hippocampus.
- Cerebellar PLP expression was down-regulated; CNP and MBP were unaffected.
- Brainstem showed inhibited PLP and MBP expression, but not CNP.
- Partial recovery of CNP and PLP was observed in the cerebral cortex with extended exposure (day 19).
Conclusions:
- Perinatal methadone exposure leads to regionally-specific disruptions in brain myelination.
- The impact on myelin proteins varies across different brain regions.
- Exposure duration influences the extent of myelin protein alterations and potential for recovery.
Abstract:
The national incidence of neonatal abstinence syndrome has dramatically increased over the last decade due to an increase in antenatal opioid exposure. Recent human and animal studies suggest that antenatal opioid exposure impacts the developing brain. The purpose of this study is to evaluate the effects of perinatal methadone exposure on myelination in multiple regions in the developing rat brain. Pregnant Sprague-Dawley rats were randomly assigned into three experimental groups and subsequently exposed to drinking water alone or drinking water containing methadone from 7 days post coitum through day 7 or through day 19 after delivery. Two male neonatal rats were randomly selected from each litter and terminated at day 19. The cerebral cortex, hippocampus, cerebellum, and brainstem were dissected and analyzed for three myelin specific proteins - CNP, PLP, and MBP - by Western blot analysis. All pups with exposure to methadone demonstrated decreased expression of CNP, PLP, and MBP in the cerebral cortex and hippocampus. In the cerebellum, PLP expression was down‑regulated without apparent alteration of CNP and MBP expression. PLP and MBP expression, but not CNP expression, were significantly inhibited in the brainstem. Compared to the pups with postnatal methadone exposure via maternal milk through day 7, partial recovery of CNP and PLP expression only occurred in the cerebral cortices of the pups exposed through day 19. The findings show that antenatal opioid exposure in rat pups is associated with regionally‑specific alterations in brain myelination that diversely affects myelin proteins.
