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Thyroid hormones mediate the impact of early-life stress on ventral tegmental area gene expression and behavior.
Bennett, Shannon N; Chang, Austin B; Rogers, Forrest D; Jones, Parker; Peña, Catherine Jensen.
Afiliación
  • Bennett SN; Princeton Neuroscience Institute, Princeton University, USA.
  • Chang AB; Princeton Neuroscience Institute, Princeton University, USA.
  • Rogers FD; Princeton Neuroscience Institute, Princeton University, USA; Department of Molecular Biology, Princeton University, USA.
  • Jones P; Princeton Neuroscience Institute, Princeton University, USA.
  • Peña CJ; Princeton Neuroscience Institute, Princeton University, USA. Electronic address: cpena@princeton.edu.
Horm Behav ; 159: 105472, 2024 03.
Article en En | MEDLINE | ID: mdl-38141539
ABSTRACT
Proper thyroid function is essential to the developing brain, including dopamine neuron differentiation, growth, and maintenance. Stress across the lifespan impacts thyroid hormone signaling and anxiety disorders and depression have been associated with thyroid dysfunction (both hypo- and hyper-active). However, less is known about how stress during postnatal development impacts thyroid function and related brain development. Our previous work in mice demonstrated that early-life stress (ELS) transiently impinged on expression of a transcription factor in dopamine neurons, Otx2, shown to be regulated by thyroid hormones. We hypothesized that thyroid hormone signaling may link experience of ELS with transcriptional dysregulation within the dopaminergic midbrain, and ultimately behavior. Here, we find that ELS transiently increases thyroid-stimulating hormone levels (inversely related to thyroid signaling) in both male and female mice at P21, an effect which recovers by adolescence. We next tested whether transient treatment of ELS mice with synthetic thyroid hormone (levothyroxine, LT4) could ameliorate the impact of ELS on sensitivity to future stress, and on expression of genes related to dopamine neuron development and maintenance, thyroid signaling, and plasticity within the ventral tegmental area. Among male mice, but not females, juvenile LT4 treatment prevented hypersensitivity to adult stress. We also found that rescuing developmental deficits in thyroid hormone signaling after ELS restored levels of some genes altered directly by ELS, and prevented alterations in expression of other genes sensitive to the second hit of adult stress. These findings suggest that thyroid signaling mediates the deleterious impact of ELS on VTA development, and that temporary treatment of hypothyroidism after ELS may be sufficient to prevent future stress hypersensitivity.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Área Tegmental Ventral / Experiencias Adversas de la Infancia Límite: Animals Idioma: En Revista: Horm Behav Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Área Tegmental Ventral / Experiencias Adversas de la Infancia Límite: Animals Idioma: En Revista: Horm Behav Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos