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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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.

元の言語English
記事番号16872
ジャーナルScientific reports
7
発行部数1
DOI
出版物ステータスPublished - 01-12-2017

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これを引用

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, 7(1), [16872]. https://doi.org/10.1038/s41598-017-17151-1