The role of glutamine in neurogenesis promoted by the green tea amino acid theanine in neural progenitor cells for brain health

Useless. No protocol specified on how much green tea we should be drinking daily. Would supplements suffice? 

The role of glutamine in neurogenesis promoted by the green tea amino acid theanine in neural progenitor cells for brain health

Author links open overlay panelYukioYoneda^ab

NobuyukiKuramoto^bcKoichiKawada^bd

https://doi.org/10.1016/j.neuint.2019.104505Get rights and content

Highlights

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Green tea intake leads to less incidence of cognitive declines in elderly people.

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 intake improves cognition abilities in patients with psychiatric disorders.

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Theanine promotes cell growth and neuronal differentiation in neural progenitor.

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Theanine up-regulates Slc38a1 transcript expression in neural progenitor.

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Theanine activates phosphorylation of mTOR in neural progenitor.

Abstract

The green tea amino acid theanine is abundant in green tea rather than black and oolong teas, which are all made of the identical tea plant “Chanoki” (Camellia sinensis). Theanine has a molecular structure close to glutamine (GLN) compared to glutamic acid (Glu), in terms of the absence of a free carboxylic acid moiety from the gamma carbon position. Theanine efficiently inhibits [³H]GLN uptake without affecting [³H]Glu uptake in rat brain synaptosomes. In contrast to GLN, however, theanine markedly stimulates the abilities to replicate and to commit to a neuronal lineage following prolonged exposure in cultured neural progenitor cells (NPCs) prepared from embryonic and adult rodent brains. Upregulation of transcript expression is found for one of the GLN transporter isoforms, Slc38a1, besides the promotion of both proliferation and neuronal commitment along with acceleration of the phosphorylation of mechanistic target of rapamycin (mTOR) and relevant downstream proteins, in murine NPCs cultured with theanine. Stable overexpression of Slc38a1 similarly facilitates both cellular replication and neuronal commitment in pluripotent embryonic carcinoma P19 cells. In P19 cells with stable overexpression of Slc38a1, marked phosphorylation is seen for mTOR and downstream proteins in a manner insensitive to further additional phosphorylation by theanine. Taken together, theanine would exhibit a novel pharmacological property to up-regulate Slc38a1 expression for activation of the intracellular mTOR signaling pathway required for neurogenesis after sustained exposure in undifferentiated NPCs in the brain. In this review, a novel neurogenic property of the green tea amino acid theanine is summarized for embryonic and adult neurogenesis with a focus on the endogenous amino acid GLN on the basis of our accumulating evidence to date.

Graphical abstract

Long-term exposure to theanine could lead to upregulation of Slc38a1 expression for the facilitated incorporation of extracellular GLN (①) in NSCs, followed by increased intracellular levels of GLN and subsequent stimulation of the exchange transport mediated by the antiporter Slc7a5/8 of intracellular GLN with extracellular EAA (②). Increased intracellular EAA levels would thus result in activation of the mTOR1 signaling pathway (③,④) required for the upregulation of different bHLH transcription factors (⑤) essential for modulation of neurogenesis (⑥) in NSCs.

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