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Selective Upregulation by Theanine of Slc38a1 Expression in Neural Stem Cell for Brain Wellness

Department of Pharmacology, Osaka University Graduate School of Dentistry, Suita 565-0871, Japan
The Institute of Prophylactic Pharmacology, Kita-Shinagawa, Shinagawa, Tokyo 140-0001, Japan
Department of Pharmacology, Chiba Institute of Science Faculty of Pharmaceutical Sciences, Chiba 288-0025, Japan
Laboratory of Molecular Pharmacology, Setsunan University Faculty of Pharmaceutical Sciences, Hirakata 573-0101, Japan
Author to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Molecules 2020, 25(2), 347;
Received: 21 November 2019 / Revised: 9 January 2020 / Accepted: 15 January 2020 / Published: 15 January 2020
(This article belongs to the Special Issue Molecular Pharmacology of Green Tea)
Theanine is an amino acid abundant in green tea with an amide moiety analogous to glutamine (GLN) rather than glutamic acid (Glu) and GABA, which are both well-known as amino acid neurotransmitters in the brain. Theanine has no polyphenol and flavonoid structures required for an anti-oxidative property as seen with catechins and tannins, which are more enriched in green tea. We have shown marked inhibition by this exogenous amino acid theanine of the uptake of [3H]GLN, but not of [3H]Glu, in rat brain synaptosomes. Beside a ubiquitous role as an endogenous amino acid, GLN has been believed to be a main precursor for the neurotransmitter Glu sequestered in a neurotransmitter pool at glutamatergic neurons in the brain. The GLN transporter solute carrier 38a1 (Slc38a1) plays a crucial role in the incorporation of extracellular GLN for the intracellular conversion to Glu by glutaminase and subsequent sequestration at synaptic vesicles in neurons. However, Slc38a1 is also expressed by undifferentiated neural progenitor cells (NPCs) not featuring a neuronal phenotype. NPCs are derived from a primitive stem cell endowed to proliferate for self-renewal and to commit differentiation to several daughter cell lineages such as neurons, astrocytes, and oligodendrocytes. In vitro culture with theanine leads to the marked promotion of the generation of new neurons together with selective upregulation of Slc38a1 transcript expression in NPCs. In this review, we will refer to a possible novel neurogenic role of theanine for brain wellness through a molecular mechanism relevant to facilitated neurogenesis with a focus on Slc38a1 expressed by undifferentiated NPCs on the basis of our accumulating findings to date. View Full-Text
Keywords: theanine; glutamine transporter; Slc38a1; neural stem cell; mTOR; neurogenesis theanine; glutamine transporter; Slc38a1; neural stem cell; mTOR; neurogenesis
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Yoneda, Y.; Kawada, K.; Kuramoto, N. Selective Upregulation by Theanine of Slc38a1 Expression in Neural Stem Cell for Brain Wellness. Molecules 2020, 25, 347.

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