Effects of thyroid disruption on neural cells stem fate in the mouse brain

Abstract

Thyroid hormones (THs), particularly T₃ and T₄, play crucial roles in neural development and maintenance by regulating neural stem cell (NSC) proliferation, differentiation, and survival. In the subventricular zone (SVZ), a neurogenic niche in the adult brain, THs influence the balance between neuronal and glial cell fate. Hypothyroidism disrupts this balance, reducing neurogenesis and increasing oligodendrocyte precursor cell (OPC) production. This can impair central nervous system repair mechanisms and olfactory function. Environmental endocrine disruptors like perfluoroalkyl substances (PFAS) exacerbate these effects. PFAS, including PFOS and PFOA, could interfere with TH signaling by altering TH synthesis, transport, and receptor interactions. In rodent models, PFOS exposure during critical window of brain development reduced myelin production and impaired remyelination processes. These effects were linked to TH modulation and were partially reversible with T3 supplementation. Research underscores the vulnerability of neurogliogenic niches to TH disruption and calls for further investigation into long-term impacts and therapeutic interventions to mitigate the adverse effects of endocrine disruptors on neural development and brain function.