Behavioral impairment in SHATI/NAT8L knockout mice via dysfunction of myelination development

Kazuyuki Sumi, Kyosuke Uno, Hiroshi Noike, Takenori Tomohiro, Yasumaru Hatanaka, Yoko Furukawa-Hibi, Toshitaka Nabeshima, Yoshiaki Miyamoto, Atsumi Nitta

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Abstract

We have identified SHATI/NAT8L in the brain of mice treated with methamphetamine. Recently, it has been reported that SHATI is N-acetyltransferase 8-like protein (NAT8L) that produces N-acetylaspatate (NAA) from aspartate and acetyl-CoA. We have generated SHATI/NAT8L knockout (Shati -/-) mouse which demonstrates behavioral deficits that are not rescued by single NAA supplementation, although the reason for which is still not clarified. It is possible that the developmental impairment results from deletion of SHATI/NAT8L in the mouse brain, because NAA is involved in myelination through lipid synthesis in oligodendrocytes. However, it remains unclear whether SHATI/NAT8L is involved in brain development. In this study, we found that the expression of Shati/Nat8l mRNA was increased with brain development in mice, while there was a reduction in the myelin basic protein (MBP) level in the prefrontal cortex of juvenile, but not adult, Shati -/- mice. Next, we found that deletion of SHATI/NAT8L induces several behavioral deficits in mice, and that glyceryltriacetate (GTA) treatment ameliorates the behavioral impairments and normalizes the reduced protein level of MBP in juvenile Shati -/- mice. These findings suggest that SHATI/NAT8L is involved in myelination in the juvenile mouse brain via supplementation of acetate derived from NAA. Thus, reduction of SHATI/NAT8L induces developmental neuronal dysfunction.

Original languageEnglish
Article number16872
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 01-12-2017

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Acetyltransferases
Knockout Mice
Proteins
Brain
Myelin Basic Protein
Acetyl Coenzyme A
Methamphetamine
Oligodendroglia
Prefrontal Cortex
Aspartic Acid
Acetates
Lipids
Messenger RNA

All Science Journal Classification (ASJC) codes

  • General

Cite this

Sumi, K., Uno, K., Noike, H., Tomohiro, T., Hatanaka, Y., Furukawa-Hibi, Y., ... Nitta, A. (2017). Behavioral impairment in SHATI/NAT8L knockout mice via dysfunction of myelination development. Scientific Reports, 7(1), [16872]. https://doi.org/10.1038/s41598-017-17151-1
Sumi, Kazuyuki ; Uno, Kyosuke ; Noike, Hiroshi ; Tomohiro, Takenori ; Hatanaka, Yasumaru ; Furukawa-Hibi, Yoko ; Nabeshima, Toshitaka ; Miyamoto, Yoshiaki ; Nitta, Atsumi. / Behavioral impairment in SHATI/NAT8L knockout mice via dysfunction of myelination development. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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abstract = "We have identified SHATI/NAT8L in the brain of mice treated with methamphetamine. Recently, it has been reported that SHATI is N-acetyltransferase 8-like protein (NAT8L) that produces N-acetylaspatate (NAA) from aspartate and acetyl-CoA. We have generated SHATI/NAT8L knockout (Shati -/-) mouse which demonstrates behavioral deficits that are not rescued by single NAA supplementation, although the reason for which is still not clarified. It is possible that the developmental impairment results from deletion of SHATI/NAT8L in the mouse brain, because NAA is involved in myelination through lipid synthesis in oligodendrocytes. However, it remains unclear whether SHATI/NAT8L is involved in brain development. In this study, we found that the expression of Shati/Nat8l mRNA was increased with brain development in mice, while there was a reduction in the myelin basic protein (MBP) level in the prefrontal cortex of juvenile, but not adult, Shati -/- mice. Next, we found that deletion of SHATI/NAT8L induces several behavioral deficits in mice, and that glyceryltriacetate (GTA) treatment ameliorates the behavioral impairments and normalizes the reduced protein level of MBP in juvenile Shati -/- mice. These findings suggest that SHATI/NAT8L is involved in myelination in the juvenile mouse brain via supplementation of acetate derived from NAA. Thus, reduction of SHATI/NAT8L induces developmental neuronal dysfunction.",
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Sumi, K, Uno, K, Noike, H, Tomohiro, T, Hatanaka, Y, Furukawa-Hibi, Y, Nabeshima, T, Miyamoto, Y & Nitta, A 2017, 'Behavioral impairment in SHATI/NAT8L knockout mice via dysfunction of myelination development', Scientific Reports, vol. 7, no. 1, 16872. https://doi.org/10.1038/s41598-017-17151-1

Behavioral impairment in SHATI/NAT8L knockout mice via dysfunction of myelination development. / Sumi, Kazuyuki; Uno, Kyosuke; Noike, Hiroshi; Tomohiro, Takenori; Hatanaka, Yasumaru; Furukawa-Hibi, Yoko; Nabeshima, Toshitaka; Miyamoto, Yoshiaki; Nitta, Atsumi.

In: Scientific Reports, Vol. 7, No. 1, 16872, 01.12.2017.

Research output: Contribution to journalArticle

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T1 - Behavioral impairment in SHATI/NAT8L knockout mice via dysfunction of myelination development

AU - Sumi, Kazuyuki

AU - Uno, Kyosuke

AU - Noike, Hiroshi

AU - Tomohiro, Takenori

AU - Hatanaka, Yasumaru

AU - Furukawa-Hibi, Yoko

AU - Nabeshima, Toshitaka

AU - Miyamoto, Yoshiaki

AU - Nitta, Atsumi

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Y1 - 2017/12/1

N2 - We have identified SHATI/NAT8L in the brain of mice treated with methamphetamine. Recently, it has been reported that SHATI is N-acetyltransferase 8-like protein (NAT8L) that produces N-acetylaspatate (NAA) from aspartate and acetyl-CoA. We have generated SHATI/NAT8L knockout (Shati -/-) mouse which demonstrates behavioral deficits that are not rescued by single NAA supplementation, although the reason for which is still not clarified. It is possible that the developmental impairment results from deletion of SHATI/NAT8L in the mouse brain, because NAA is involved in myelination through lipid synthesis in oligodendrocytes. However, it remains unclear whether SHATI/NAT8L is involved in brain development. In this study, we found that the expression of Shati/Nat8l mRNA was increased with brain development in mice, while there was a reduction in the myelin basic protein (MBP) level in the prefrontal cortex of juvenile, but not adult, Shati -/- mice. Next, we found that deletion of SHATI/NAT8L induces several behavioral deficits in mice, and that glyceryltriacetate (GTA) treatment ameliorates the behavioral impairments and normalizes the reduced protein level of MBP in juvenile Shati -/- mice. These findings suggest that SHATI/NAT8L is involved in myelination in the juvenile mouse brain via supplementation of acetate derived from NAA. Thus, reduction of SHATI/NAT8L induces developmental neuronal dysfunction.

AB - We have identified SHATI/NAT8L in the brain of mice treated with methamphetamine. Recently, it has been reported that SHATI is N-acetyltransferase 8-like protein (NAT8L) that produces N-acetylaspatate (NAA) from aspartate and acetyl-CoA. We have generated SHATI/NAT8L knockout (Shati -/-) mouse which demonstrates behavioral deficits that are not rescued by single NAA supplementation, although the reason for which is still not clarified. It is possible that the developmental impairment results from deletion of SHATI/NAT8L in the mouse brain, because NAA is involved in myelination through lipid synthesis in oligodendrocytes. However, it remains unclear whether SHATI/NAT8L is involved in brain development. In this study, we found that the expression of Shati/Nat8l mRNA was increased with brain development in mice, while there was a reduction in the myelin basic protein (MBP) level in the prefrontal cortex of juvenile, but not adult, Shati -/- mice. Next, we found that deletion of SHATI/NAT8L induces several behavioral deficits in mice, and that glyceryltriacetate (GTA) treatment ameliorates the behavioral impairments and normalizes the reduced protein level of MBP in juvenile Shati -/- mice. These findings suggest that SHATI/NAT8L is involved in myelination in the juvenile mouse brain via supplementation of acetate derived from NAA. Thus, reduction of SHATI/NAT8L induces developmental neuronal dysfunction.

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