Thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata

Abstract Thiamine is critical for cellular function, as its phosphorylated and active form, thiamine diphosphate (TDP), acts as coenzyme for three key enzymes in glucose metabolism. Mutations in thiamine transporter, TDP synthesizing enzyme or carrier, including solute carrier family 19 member 3 (SL...

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Autores principales:	Huimin Liu, Shaoming Sang, Yuan Lu, Zhongfeng Wang, Xiang Yu, Chunjiu Zhong
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a761fa752f69452f9774ef8c2866b610
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spelling	oai:doaj.org-article:a761fa752f69452f9774ef8c2866b6102021-12-02T12:32:04ZThiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata10.1038/s41598-017-05476-w2045-2322https://doaj.org/article/a761fa752f69452f9774ef8c2866b6102017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05476-whttps://doaj.org/toc/2045-2322Abstract Thiamine is critical for cellular function, as its phosphorylated and active form, thiamine diphosphate (TDP), acts as coenzyme for three key enzymes in glucose metabolism. Mutations in thiamine transporter, TDP synthesizing enzyme or carrier, including solute carrier family 19 member 3 (SLC19A3), thiamine pyrophosphokinase (TPK1) and solute carrier family 25 member 19 (SLC25A19), have been associated with developmental neurological disorders, including microcephaly and Leigh syndrome. However, little is known about how thiamine metabolism regulates neuronal morphology at the cellular level. Here, using primary rat hippocampal neuronal cultures, we showed that reducing the expression of Tpk1, Slc25a19 or Slc19a3 in individual neurons significantly reduced dendrite complexity, as measured by total dendritic branch tip number (TDBTN) and total dendritic branch length (TDBL). The specificity of the RNAi effects were verified by overexpression of RNAi resistant human constructs. Importantly, changes in both TDBTN and TDBL tightly correlated with reduction in soma size, demonstrating coordinated regulation of soma and dendrite growth by thiamine. The requirement of thiamine metabolism for coordinated somata and dendrite growth is highly consistent with the microcephaly and neurodegenerative phenotypes observed in thiamine loss-of-function diseases.Huimin LiuShaoming SangYuan LuZhongfeng WangXiang YuChunjiu ZhongNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Huimin Liu Shaoming Sang Yuan Lu Zhongfeng Wang Xiang Yu Chunjiu Zhong Thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata
description	Abstract Thiamine is critical for cellular function, as its phosphorylated and active form, thiamine diphosphate (TDP), acts as coenzyme for three key enzymes in glucose metabolism. Mutations in thiamine transporter, TDP synthesizing enzyme or carrier, including solute carrier family 19 member 3 (SLC19A3), thiamine pyrophosphokinase (TPK1) and solute carrier family 25 member 19 (SLC25A19), have been associated with developmental neurological disorders, including microcephaly and Leigh syndrome. However, little is known about how thiamine metabolism regulates neuronal morphology at the cellular level. Here, using primary rat hippocampal neuronal cultures, we showed that reducing the expression of Tpk1, Slc25a19 or Slc19a3 in individual neurons significantly reduced dendrite complexity, as measured by total dendritic branch tip number (TDBTN) and total dendritic branch length (TDBL). The specificity of the RNAi effects were verified by overexpression of RNAi resistant human constructs. Importantly, changes in both TDBTN and TDBL tightly correlated with reduction in soma size, demonstrating coordinated regulation of soma and dendrite growth by thiamine. The requirement of thiamine metabolism for coordinated somata and dendrite growth is highly consistent with the microcephaly and neurodegenerative phenotypes observed in thiamine loss-of-function diseases.
format	article
author	Huimin Liu Shaoming Sang Yuan Lu Zhongfeng Wang Xiang Yu Chunjiu Zhong
author_facet	Huimin Liu Shaoming Sang Yuan Lu Zhongfeng Wang Xiang Yu Chunjiu Zhong
author_sort	Huimin Liu
title	Thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata
title_short	Thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata
title_full	Thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata
title_fullStr	Thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata
title_full_unstemmed	Thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata
title_sort	thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a761fa752f69452f9774ef8c2866b610
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Thiamine metabolism is critical for regulating correlated growth of dendrite arbors and neuronal somata

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