Absence of Thyroid Hormone Induced Delayed Dendritic Arborization in Mouse Primary Hippocampal Neurons Through Insufficient Expression of Brain-Derived Neurotrophic Factor.
Absence of Thyroid Hormone Induced Delayed Dendritic Arborization in Mouse Primary Hippocampal Neurons Through Insufficient Expression of Brain-Derived Neurotrophic Factor.
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甲状腺激素缺乏通过脑源性神经营养因子表达不足诱导小鼠原代海马神经元延迟树突状树枝形成。
DOI：
10.3389/fendo.2021.629100
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发表时间：
2021
影响因子：
5.2
通讯作者：
Koibuchi N
中科院分区：
文献类型：
--
作者：
Yajima H;Amano I;Ishii S;Sadakata T;Miyazaki W;Takatsuru Y;Koibuchi N
甲状腺激素（TH）在大脑发育中起着重要作用。早期生活中的TH缺乏会导致海马体严重的发育障碍。然而，在发育中的海马体中，TH的作用机制仍然很大程度上是未知的。在本研究中，我们在神经元补充剂21 （NS21）的基础上制备了不含3,5,3 ' -三碘- 1 -甲状腺原氨酸（T3）的神经元补充剂，利用原代培养的神经元检测TH对发育中的海马的影响。比较不含T3的培养基（-T3组）和添加T3的培养基（+T3组）对神经元的影响。在离体7、10和14天（DIV）进行形态计量学分析和RT-qPCR。10 DIV时，-T3组树突树枝化减少。这种差异在7和14 DIV上没有观察到。脑源性神经营养因子（Bdnf） mRNA水平在-T3组在10 DIV上也显著降低。然后，我们通过免疫细胞化学和Western blot分析证实了Bdnf受体磷酸化神经营养酪氨酸激酶2型（NTRK2， TRKB）在10 DIV上的蛋白水平。与+T3组相比，-T3组磷酸化的NTRK2水平在10 DIV上显著下降。考虑到BDNF在神经发育中的作用，我们通过在8和9 DIV上添加BDNF来检测其参与程度。添加10 ng/ml BDNF可以恢复10 DIV上T3缺乏引起的抑制树突生长。我们发现，缺乏TH会导致初级海马神经元发育迟缓，可能是由于BDNF表达减少引起的。因此，BDNF可能在th调控的树突发生中发挥作用。
Thyroid hormone (TH) plays important roles in the developing brain. TH deficiency in early life leads to severe developmental impairment in the hippocampus. However, the mechanisms of TH action in the developing hippocampus are still largely unknown. In this study, we generated 3,5,3’-tri-iodo-l-thyronine (T3)-free neuronal supplement, based on the composition of neuronal supplement 21 (NS21), to examine the effect of TH in the developing hippocampus using primary cultured neurons. Effects of TH on neurons were compared between cultures in this T3-free culture medium (-T3 group) and a medium in which T3 was added (+T3 group). Morphometric analysis and RT-qPCR were performed on 7, 10, and 14 days in vitro (DIV). On 10 DIV, a decreased dendrite arborization in -T3 group was observed. Such difference was not observed on 7 and 14 DIV. Brain-derived neurotrophic factor (Bdnf) mRNA levels also decreased significantly in -T3 group on 10 DIV. We then confirmed protein levels of phosphorylated neurotrophic tyrosine kinase type 2 (NTRK2, TRKB), which is a receptor for BDNF, on 10 DIV by immunocytochemistry and Western blot analysis. Phosphorylated NTRK2 levels significantly decreased in -T3 group compared to +T3 group on 10 DIV. Considering the role of BDNF on neurodevelopment, we examined its involvement by adding BDNF on 8 and 9 DIV. Addition of 10 ng/ml BDNF recovered the suppressed dendrite arborization induced by T3 deficiency on 10 DIV. We show that the lack of TH induces a developmental delay in primary hippocampal neurons, likely caused through a decreased Bdnf expression. Thus, BDNF may play a role in TH-regulated dendritogenesis.
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影响因子：
5.2
作者：
Ariyani W;Iwasaki T;Miyazaki W;Khongorzul E;Nakajima T;Kameo S;Koyama H;Tsushima Y;Koibuchi N
通讯作者：
Koibuchi N
影响因子：
2.9
作者：
BANKER, GA;COWAN, WM
通讯作者：
COWAN, WM
影响因子：
3.5
作者：
Impey, Soren;Davare, Monika;Lasiek, Adam;Fortin, Dale;Ando, Hideaki;Varlamova, Olga;Obrietan, Karl;Soderling, Thomas R.;Goodman, Richard H.;Wayman, Gary A.
通讯作者：
Wayman, Gary A.
影响因子：
3.3
作者：
Jacobs, S.;Cheng, C.;Doering, L. C.
通讯作者：
Doering, L. C.
影响因子：
4.8
作者：
Gilbert, M. E.;Sanchez-Huerta, K.;Wood, C.
通讯作者：
Wood, C.