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2 Acta Neurobiologiae Experimentalis

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Effects of maternal thyroid hormone deficiency on differentiation of mesenchymal stem cells in CSF‑exposed neonatal Wistar rats

100%

Mafikandi V. , Roodbari N. H. , Nabiuni M. , Yaghmaei P.

2019

tom 79

nr 3

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.

Investigating the synergic effects of valproic acid and crocin on BDNF and GDNF expression in epidermal neural crest stem cells

88%

Baharvand Z. , Nabiuni M. , Tahmaseb M. , Amini E. , Pandamooz S.

nr 1

Following nerve tissue damage, various events, such as inflammatory responses, microglial activation, endoplasmic reticulum stress, and apoptosis, can occur, which all lead to cell death, prevent axonal growth, and cause axonal circumvolution. So far, several researchers have tended to adopt strategies to reduce the harmful conditions associated with neurological disorders, and stem‑cell‑based therapy is one of those promising strategies. Epidermal neural crest stem cells (EPI‑NCSCs) are a type of stem cell that has widely been employed for the treatment of various neurological disorders. It has been suggested that these stem cells perform their supportive actions primarily through the release of different neurotrophic factors. Hence, in this study, the neuroprotective impacts of valproic acid (VPA) and crocin were evaluated on the mRNA expression levels of brain‑derived neurotrophic factor (BDNF) and glial‑cell‑derived neurotrophic factor (GDNF) in EPI‑NCSCs. In this research, we isolated EPI‑NCSCs from the hair follicles of the rat whisker pad. Then, the cells were treated with different concentrations of VPA and crocin for 72 h. Subsequently, an MTT assay was performed to define the suitable concentrations of drugs. Finally, real‑time PCR was performed to evaluate the mRNA expression levels of BDNF and GDNF in these stem cells. The results of the MTT assay showed that the treatment of EPI‑NCSCs with 1 mM VPA and 1.5 mM crocin, and the co‑treatment with 1 mM VPA and 500 µM crocin, led to the survival and proliferation of these stem cells. Moreover, the real‑time PCR results revealed that both VPA and crocin, both individually and in combination, can significantly increase the expression levels of BDNF and GDNF in EPI‑NCSCs. According to the findings of this study, both VPA and crocin, alone and in combination, are potential candidates for enhancing the capacity of EPI‑NCSCs to differentiate into neural lineages. Therefore, the co‑treatment of EPI‑NCSCs with these drugs can be employed for the treatment of various neurological disorders, such as spinal cord injury.