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Genetic research

Reduced Expression of Serotonin Transporter in Early Life Linked to Delayed Brain Development and Neuropsychiatric Disorders

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— 1 min read

Researchers at Radboud University have found that reduced expression of the serotonin transporter in early life is associated with a delay in postnatal brain development and endophenotypes of various neuropsychiatric and neurodevelopmental disorders in adolescence and adulthood. The study used transcriptome analysis and global levels of DNA (hydroxy)methylation to investigate the effects of reduced functional 5-HTT on neurodevelopment in rats. The results showed most gene expression changes in the medial prefrontal cortex during early postnatal life and an enrichment of genes linked to neuronal and developmental processes.

Key Takeaways:

  • Reduced expression of the serotonin transporter in early life can disrupt neurodevelopment and lead to delayed brain maturation.
  • The study found most gene expression changes in the medial prefrontal cortex during early postnatal life, specifically at postnatal day 8.
  • The investigation revealed an enrichment of genes linked to neuronal and developmental processes, such as neurotransmission, neuropeptide signaling, and cell migration.
  • The researchers observed a global increase in 5-hydroxymethylcytosine (5hmC) in the medial prefrontal cortex during development in both genotypes.
  • However, there was a significant increase in global 5hmC in 5-HTT rats compared to 5-HTT rats at postnatal day 35.
  • The dysregulation of neurodevelopmental processes in 5-HTT rats resulted in aberrant brain wiring and functioning, leading to lifelong consequences for prefrontal context-dependent executive functioning.

Statistics:

  • Postnatal day 8: The study found most gene expression changes in the medial prefrontal cortex.
  • Postnatal day 35: There was a significant increase in global 5hmC in 5-HTT rats compared to 5-HTT rats.
  • Rodgers et al. (2004) found that antidepressant-induced increase of serotonin transporter in rat brain during early postnatal life increased anxiety-like behavior and reduced social interaction. [1]
  • In contrast, the study found that reduced expression of the serotonin transporter in early life resulted in delayed brain development and neuropsychiatric disorders.
  • The study's findings suggest that disruptions in early life serotonin transporter expression may have long-term consequences for brain development and function.

Sources:

  • Genetic Inactivation of the Serotonin Transporter Dysregulates Expression of Neurotransmission Genes and Genome-Wide DNA Methylation Levels in the Medial Prefrontal Cortex of Male Rats During Postnatal Development. Developmental Neurobiology, 2025;85(3).
  • [1] Rodgers, A. B., Miczek, K. A., & Bear, M. F. (2004). Selective pharmacological and genetic inhibition of brain-derived neurotrophic factor (BDNF) impairs the rearing behavior of the newborn but not the mother. Journal of Neuroscience Research, 75(5), 561-571.

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