title: Induction of neuronal axon outgrowth by Shati/Nat8l by energy metabolism in mice cultured neurons.
abstract: A novel N-acetyltransferase, Shati/Nat8l, was identified in the nucleus accumbens of mice repeatedly treated with methamphetamine (METH). Shati/Nat8l has been reported to inhibit the pharmacological action induced by METH. Shati/Nat8l produces N-acetylaspartate from aspartate and acetyl-CoA. Previously, we reported that overexpression of Shati/Nat8l in nucleus accumbens attenuates the response to METH by N-acetylaspartylglutamate (which is derived from N-acetylaspartate)-mGluR3 signaling in the mice brain. In the present study, to clarify the type of cells that produce Shati/Nat8l, we carried out in-situ hybridization for the detection of Shati/Nat8l mRNA along with immunohistochemical studies using serial sections of mice brain. Shati/Nat8l mRNA was detected in neuronal cells, but not in astrocytes or microglia cells. Next, we investigated the function of Shati/Nat8l in the neuronal cells in mice brain; then, we used an adeno-associated virus vector containing Shati/Nat8l for transfection and overexpression of Shati/Nat8l protein into the primary cultured neurons to investigate the contribution toward the neuronal activity of Shati/Nat8l. Overexpression of Shati/Nat8l in the mice primary cultured neurons induced axonal growth, but not dendrite elongation at day 1.5 (DIV). This finding indicated that Shati/Nat8l contributes toward neuronal development. LY341495, a selective group II mGluRs antagonist, did not abolish this axonal growth, and N-acetylaspartylglutamate itself did not abolish axon outgrowth in the same cultured system. The cultured neurons overexpressing Shati/Nat8l contained high ATP, suggesting that axon outgrowth is dependent on energy metabolism. This study shows that Shati/Nat8l in the neuron may induce axon outgrowth by ATP synthesis and not through mGluR3 signaling.
authors.affiliation: aDepartment of Pharmaceutical Therapy and Neuropharmacology, Faculty of Pharmaceutical Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama bDepartment of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya cDivision of Neurology, Department of Medicine, Jichi Medical University, Shimotsuke dNabeshima Laboratory, Faculty of Pharmacy, Meijo University eNPO Japnese Drug Organization of Apptovalate Use and Research, Nagoya, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Sumi
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Uno
authors.forename: Shohei
authors.initials: S
authors.lastname: Matsumura
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Yoko
authors.initials: Y
authors.lastname: Furukawa-Hibi
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Muramatsu
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
authors.forename: Atsumi
authors.initials: A
authors.lastname: Nitta
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism*; D000255:Adenosine Triphosphate; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism; D004734:Energy Metabolism; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000378:metabolism
chemical_list: D000255:Adenosine Triphosphate; D000123:Acetyltransferases; C521704:Shati protein, mouse