Abstract
Cerebrospinal fluid (CSF) contains growth and neurotrophic factors which regulate proliferation, differentiation, and neurogenesis. Thyroid hormones play a crucial role in the development of the nervous system and hypothyroidism during development of embryos leads to defects in the nervous system. This study aimed to survey the effects of rat neonatal CSF collected from induced hypothyroid mothers on differentiation of bone marrow mesenchymal stem cells (BM-MSCs). We hypothesized that hypothyroidism affected levels of growth factor in CSF. To induce hypothyroidism, pregnant Wistar rats received methimazole at the third day of gestation. BM-MSCs were obtained from rat femurs and tibias and cultured in medium. CSF was collected from the cisterna magna of newborn rats, and cells were subsequently exposed to CSF with concentrations of 5,7, and 10 /100 (v/v) for 72 h. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and real time polymerase chain reaction (RT-PCR) were used to quantify the cell viability and analyze the expression of neural markers, respectively. Our morphological studies showed that treatment with hypothyroidism CSF (HTH-CSF) resulted in a significant decrease in neurite growth and proliferation as compared to normal CSF (N-CSF). RT-PCR analysis also showed a significant decrease in expression of neural markers (i.e., Nestin, Neurod-1, NeuN) in cells treated with HTH-CSF as compared with the N-CSF group. The most effective concentration of CSF for BM-MSC differentiation was 5% (V/V). Our results showed a significant decrease in differentiation of BM-MSCs in the presence of neonatal CSF of hypothyroid mothers compared with neonatal CSF of healthy mothers. Thus, thyroid hormones are essential in neural development and hypothyroid defects can affect development of the neonatal brain.
Highlights
Thyroid hormone and its active de‐ iodinated derivative, 3,5,3‐triiodo‐L‐thyronine (T3) are important regulators for neural development of ver‐ tebrates which function in the brain by binding to T3 nuclear receptors (Chatonnet et al, 2011)
Cells that were treated with 5% HTH‐Cerebrospinal fluid (CSF) showed a more significant in‐ crease in viability as compared to cells treated with 7% and 10% hypothyroidism CSF (HTH‐CSF) (Fig. 1)
Our results demonstrated that Nestin expression decreased in bone marrow mesenchymal stem cells (BM‐MSCs) treated with HTH‐CSF as compared with normal CSF (N‐CSF)
Summary
Thyroid hormone (thyroxine, T4) and its active de‐ iodinated derivative, 3,5,3‐triiodo‐L‐thyronine (T3) are important regulators for neural development of ver‐ tebrates which function in the brain by binding to T3 nuclear receptors (Chatonnet et al, 2011). Thy‐ roid hormones pass through the placenta and the growing embryo relies on the mother for thyroid hormones during the first half of pregnancy (Sahay et al, 2012). When pregnancy is accompanied by hypothy‐ roidism, an array of unexpected problems are possible for both the mother and fetus (Sahay and Nagesh, 2012). T4 and T3 ligand regulate neural differentiation and control dendritic and axonal growth, neural cell migra‐ tion, synaptogenesis, myelination, and signaling (Ber nal, 2015). Previous investigations have reported that hypothyroidism during critical phases of brain develop‐ ment in fetal and neonatal life lead to various changes in the pattern of migration, and result in reduced cell number and myelination in cerebellum, neocortex, and
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