Perinatal Fluoxetine Exposure Has No Major Effect on Myelin-Associated Glycoprotein and Myelin Basic Protein Levels in Auditory Brain Regions

TL;DR

Exposure to fluoxetine during pregnancy and early life does not significantly affect myelin development in brain regions related to hearing in rats.

Contribution

The study shows that perinatal fluoxetine exposure does not disrupt myelin development in auditory brain regions, despite dynamic changes during maturation.

Findings

Fluoxetine exposure had no major effect on myelin markers in auditory brain regions.

Myelination changes occurred between PND21 and PND35, varying by brain region.

Changes in myelination were region- and age-dependent but not influenced by fluoxetine.

Abstract

Hearing is important for social interactions and learning, but both hearing loss and changes in brain chemistry can affect how the brain develops. One important brain chemical is serotonin, which helps regulate mood and development. Some medications that increase serotonin, such as fluoxetine (commonly prescribed as an antidepressant), are sometimes taken during pregnancy, but it is not clear how they might influence brain development related to hearing. In this study, we tested whether exposure to fluoxetine during pregnancy and early life affected how the brain produces myelin, a protective coating that helps nerve cells transmit signals efficiently. We studied young rats at two different ages and examined brain areas important for hearing and communication. We found that fluoxetine had no major effect on myelin development. However, we did observe changes in myelin as the brain matured, and these changes were different across brain regions. These findings show that brain development in hearing pathways is highly dynamic during early life, but exposure to fluoxetine alone may not disrupt this process. Understanding how medications and hearing-related brain development interact is important for making informed decisions about maternal health and child development.

Hearing loss and serotonergic dysfunction both impact social and cognitive behaviors, yet their neurobiological interplay remains poorly understood. This study investigated whether perinatal fluoxetine exposure alters myelination in (auditory) brain regions during development. Female Wistar rats received 10 mg/kg fluoxetine from gestational day 1 until postnatal day (PND)21. Brain tissue was collected from male offspring at PND21 and PND35. Myelination was assessed via immunohistochemical analysis of Myelin-Associated Glycoprotein (MAG) and Myelin Basic Protein (MBP) in the auditory cortex, inferior colliculus, and corpus callosum. MAG+ cell counts, MBP+ area, and MBP fluorescence intensity were quantified. No major effects of fluoxetine were observed on myelin markers in any brain region or developmental stage. However, changes in myelination emerged between PND21 and PND35. MAG+ cell density declined in the inferior colliculus but remained stable in the auditory cortex. MBP+ area decreased over time in both the corpus callosum and auditory cortex, while MBP fluorescence intensity increased in the corpus callosum. These results suggest that myelination changes between PND21 and PND35 are region- and age-dependent and not altered by fluoxetine. These findings highlight the dynamic nature of postnatal myelination and suggest that serotonergic alterations alone may be insufficient to disrupt structural maturation in auditory regions.

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