Reduced Hippocampal Brain-Derived Neurotrophic Factor (BDNF) in Neonatal Rats after Prenatal Exposure to Propylthiouracil (PTU)

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.

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Thyroid hormone and central nervous system development

Journal of Endocrinology ◽

10.1677/joe.0.1650001 ◽

2000 ◽

Vol 165 (1) ◽

pp. 1-8 ◽

Cited By ~ 123

Author(s):

S Chan ◽

MD Kilby

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Thyroid Hormone ◽

System Development ◽

Nervous System Development ◽

Central Nervous System Development

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Brain-Derived Neurotrophic Factor in Central Nervous System Myelination: A New Mechanism to Promote Myelin Plasticity and Repair

International Journal of Molecular Sciences ◽

10.3390/ijms19124131 ◽

2018 ◽

Vol 19 (12) ◽

pp. 4131 ◽

Cited By ~ 21

Author(s):

Jessica Fletcher ◽

Simon Murray ◽

Junhua Xiao

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Neural Development ◽

Neurotrophic Factor ◽

Molecular Mechanisms ◽

Demyelinating Disease ◽

Cell Types ◽

Brain Derived Neurotrophic Factor ◽

Future Research ◽

Health And Disease

Brain-derived neurotrophic factor (BDNF) plays vitally important roles in neural development and plasticity in both health and disease. Recent studies using mutant mice to selectively manipulate BDNF signalling in desired cell types, in combination with animal models of demyelinating disease, have demonstrated that BDNF not only potentiates normal central nervous system myelination in development but enhances recovery after myelin injury. However, the precise mechanisms by which BDNF enhances myelination in development and repair are unclear. Here, we review some of the recent progress made in understanding the influence BDNF exerts upon the myelinating process during development and after injury, and discuss the cellular and molecular mechanisms underlying its effects. In doing so, we raise new questions for future research.

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The Monocarboxylate Transporter 8 Linked to Human Psychomotor Retardation Is Highly Expressed in Thyroid Hormone-Sensitive Neuron Populations

Endocrinology ◽

10.1210/en.2004-1179 ◽

2005 ◽

Vol 146 (4) ◽

pp. 1701-1706 ◽

Cited By ~ 176

Author(s):

Heike Heuer ◽

Michael K. Maier ◽

Sandra Iden ◽

Jens Mittag ◽

Edith C. H. Friesema ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Thyroid Hormone ◽

System Development ◽

Perinatal Period ◽

Psychomotor Retardation ◽

Nervous System Development ◽

Monocarboxylate Transporter ◽

Target Cells

Abstract Recent genetic analysis in several patients presenting a severe form of X-linked psychomotor retardation combined with abnormal thyroid hormone (TH) levels have revealed mutations or deletions in the gene of the monocarboxylate transporter 8 (MCT8). Because in vitro MCT8 functions as a TH transporter, the complex clinical picture of these patients indicated an important role for MCT8 in TH-dependent processes of brain development. To provide a clue to the cellular function of MCT8 in brain, we studied the expression of MCT8 mRNA in the murine central nervous system by in situ hybridization histochemistry. In addition to the choroid plexus structures, the highest transcript levels were found in neo- and allocortical regions (e.g. olfactory bulb, cerebral cortex, hippocampus, and amygdala), moderate signal intensities in striatum and cerebellum, and low levels in a few neuroendocrine nuclei. Colocalization studies revealed that MCT8 is predominantly expressed in neurons. Together with the spatiotemporal expression pattern of MCT8 during the perinatal period, these results strongly indicate that MCT8 plays an important role for proper central nervous system development by transporting TH into neurons as its main target cells.

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THYROID HORMONES IN FETAL CENTRAL NERVOUS SYSTEM DEVELOPMENT

Fetal and Maternal Medicine Review ◽

10.1017/s0965539503001086 ◽

2003 ◽

Vol 14 (3) ◽

pp. 177-208 ◽

Cited By ~ 21

Author(s):

SHIAO CHAN ◽

JOANNE ROVET

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Thyroid Hormone ◽

Thyroid Hormones ◽

Normal Development ◽

Neonatal Period ◽

System Development ◽

Nervous System Development ◽

Hormone Deficiency ◽

Central Nervous System Development

Thyroid hormones are important for normal development of the human central nervous system (CNS). It is well established in children with congenital hypothyroidism that neonatal thyroid hormone deficiency significantly impairs subsequent neurodevelopment. In these children, the period of thyroid hormone insufficiency, which can begin in utero and extend until thyroid status is restored to normal in the neonatal period, determines the severity and type of defect manifested. While prompt and optimal thyroid hormone supplementation, following newborn screening is associated with far improved outcome and near normal development, subtle specific neurodevelopmental differences are still detectable compared to euthyroid controls. Because the particular impairments reflect the exact period of thyroid hormone insufficiency postnatally, as well as during gestation, this implies that brain development is not only thyroid hormone dependent in the neonatal period, but also prior to birth.

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Antenatal Glucocorticoids Supplementation and Central Nervous System Development

Current Drug Metabolism ◽

10.2174/1389200211314020002 ◽

2013 ◽

Vol 14 (2) ◽

pp. 160-166

Author(s):

Diego Gazzolo ◽

Laura D. Serpero ◽

Alessandro Frigiola ◽

Raul Abella ◽

Alessandro Giamberti ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

System Development ◽

Nervous System Development ◽

Central Nervous System Development

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Incorporation of 5-Bromo-2′-deoxyuridine into DNA and Proliferative Behavior of Cerebellar Neuroblasts: All That Glitters Is Not Gold

Cells ◽

10.3390/cells10061453 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1453

Author(s):

Joaquín Martí-Clúa

Keyword(s):

Central Nervous System ◽

Nervous System ◽

System Development ◽

Nervous System Development ◽

Current Data ◽

Cellular Mechanisms ◽

Dividing Cells ◽

The Central Nervous System ◽

Repeated Doses ◽

Pyrimidine Analog

The synthetic halogenated pyrimidine analog, 5-bromo-2′-deoxyuridine (BrdU), is a marker of DNA synthesis. This exogenous nucleoside has generated important insights into the cellular mechanisms of the central nervous system development in a variety of animals including insects, birds, and mammals. Despite this, the detrimental effects of the incorporation of BrdU into DNA on proliferation and viability of different types of cells has been frequently neglected. This review will summarize and present the effects of a pulse of BrdU, at doses ranging from 25 to 300 µg/g, or repeated injections. The latter, following the method of the progressively delayed labeling comprehensive procedure. The prenatal and perinatal development of the cerebellum are studied. These current data have implications for the interpretation of the results obtained by this marker as an index of the generation, migration, and settled pattern of neurons in the developing central nervous system. Caution should be exercised when interpreting the results obtained using BrdU. This is particularly important when high or repeated doses of this agent are injected. I hope that this review sheds light on the effects of this toxic maker. It may be used as a reference for toxicologists and neurobiologists given the broad use of 5-bromo-2′-deoxyuridine to label dividing cells.

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