THE IMPACT OF PRENATAL METHADONE EXPOSURE ON RAT FOETAL OLIGODENDROCYTE PROGENITOR CELL ABUNDANCE AND MIGRATION: MITIGATION BY SODIUM BUTYRATE SUPPLEMENTATION

Prenatal exposure to opioids increases the risk of cognitive and behavioural problems. This has been linked to white matter alterations present at birth. However, the timing and mechanisms underlying disrupted myelination remain poorly understood, and therapeutic interventions are limited. Sodium butyrate (NaB), a short-chain fatty acid, has been associated with protection of oligodendrocyte lineage cells and myelination, indicating therapeutic potential in the context of prenatal opioid exposure. This study aimed to (1) confirm the impact of maternal methadone exposure and (2) evaluate whether NaB co-administration protects oligodendrocyte progenitor cell (OPC) abundance and spatial distribution in the late foetal rat brain. Pregnant Sprague Dawley rats were assigned to one of four treatment conditions: Sham/Vehicle (n=6), Methadone/Vehicle (n=6), Sham/NaB (n=5), and Methadone/NaB (n=6). Methadone was administered via osmotic minipump (9mg/kg/day) and NaB (1.5% weight/volume) was administered via drinking water. Foetal brains were collected at gestational day 20 and processed for immunohistochemical analysis. OPCs expressing the transcription factor Olig2 were quantified within ventricular and cortical regions to assess potential changes in OPC abundance and migration patterns. Prenatal methadone exposure significantly reduced head size in male foetal pups compared to sham controls. Analyses also indicated sex-, treatment-, and region-dependent differences in Olig2-positive cell abundance and distribution, suggesting modulation by NaB. These findings highlight sex-specific vulnerability to prenatal methadone exposure and provide insight into early disruptions in oligodendrocyte development that may later affect myelination. NaB is a promising candidate for preventing these methadone-induced deficits in OPC abundance and spatial distribution.