title: Reduced hippocampal brain-derived neurotrophic factor (BDNF) in neonatal rats after prenatal exposure to propylthiouracil (PTU).
abstract: Thyroid hormone is critical for central nervous system development. Fetal hypothyroidism leads to reduced cognitive performance in offspring as well as other effects on neural development in both humans and experimental animals. The nature of these impairments suggests that thyroid hormone may exert its effects via dysregulation of the neurotrophin brain-derived neurotrophic factor (BDNF), which is critical to normal development of the central nervous system and has been implicated in neurodevelopmental disorders. The only evidence of BDNF dysregulation in early development, however, comes from experimental models in which severe prenatal hypothyroidism occurred. By contrast, milder prenatal hypothyroidism has been shown to alter BDNF levels and BDNF-dependent functions only much later in life. We hypothesized that mild experimental prenatal hypothyroidism might lead to dysregulation of BDNF in the early postnatal period. BDNF levels were measured by ELISA at 3 or 7 d after birth in different regions of the brains of rats exposed to propylthiouracil (PTU) in the drinking water. The dose of PTU that was used induced mild maternal thyroid hormone insufficiency. Pups, but not the parents, exhibited alterations in tissue BDNF levels. Hippocampal BDNF levels were reduced at both d 3 and 7, but no significant reductions were observed in either the cerebellum or brain stem. Unexpectedly, more males than females were born to PTU-treated dams, suggesting an effect of PTU on sex determination. These results support the hypothesis that reduced hippocampal BDNF levels during early development may contribute to the adverse neurodevelopmental effects of mild thyroid hormone insufficiency during pregnancy.
authors.affiliation: The Nathan Kline Institute for Psychiatric Research, Center for Dementia Research, Orangeburg, New York 10962, USA.
authors.forename: Goutam
authors.initials: G
authors.lastname: Chakraborty
authors.forename: Alejandra
authors.initials: A
authors.lastname: Magagna-Poveda
authors.forename: Carolyn
authors.initials: C
authors.lastname: Parratt
authors.forename: Jason G
authors.initials: JG
authors.lastname: Umans
authors.forename: Neil J
authors.initials: NJ
authors.lastname: MacLusky
authors.forename: Helen E
authors.initials: HE
authors.lastname: Scharfman
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018811:Maternal Exposure; D011247:Pregnancy; D011270:Pregnancy, Animal; D011441:Propylthiouracil / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000172:deficiency / Q000378:metabolism; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D013963:Thyroid Hormones; D011441:Propylthiouracil