Abstract
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.
Highlights
The prevailing view is that glutamic acid (Glu) plays a dual role in the mammalian central nervous system as an excitotoxic neurotoxin and as an excitatory neurotransmitter through a variety of ionotropic and metabotropic Glu receptor subtypes, besides a ubiquitous role as an energy source and a protein constituent in most eukaryotic cells
Sustained exposure to theanine would lead to selective upregulation of solute carrier 38a1 (Slc38a1) expression toward the increased intracellular GLN level, followed by facilitated incorporation of extracellular essential amino acids (EAAs) in exchange of intracellular GLN in primitive neural stem cells (NSCs)/neural progenitor cells (NPCs) only, but not in daughter cells such as neurons and astrocytes
By contrast, theanine should suppress the replenishment of neurotransmitter pools of inhibitory GABA as well as excitatory Glu through a mechanism relevant to inhibition of the incorporation mediated by different isoforms of glutamine transporter (GLNT) of extracellular GLN
Summary
The prevailing view is that glutamic acid (Glu) plays a dual role in the mammalian central nervous system as an excitotoxic neurotoxin and as an excitatory neurotransmitter through a variety of ionotropic and metabotropic Glu receptor subtypes, besides a ubiquitous role as an energy source and a protein constituent in most eukaryotic cells. During the in vitro culture in the presence of several growth factors of NPCs prepared from neocortex of embryonic rats [16] and mice [17], in addition to adult mouse hippocampus [18,19], round spheres named neurospheres are invariably formed by clustered dividing cells along with an increasing size proportional to the days in culture These neurospheres are enriched of cells immunoreactive for a progenitor marker protein, but not for either a neuronal marker or an astrocytic marker. The neurosphere size is adequately increasing in proportion to the days in culture as an index of the proliferative activity, while the differentiation activity is quantitatively estimated by counting the number of cells immunoreactive for each marker protein over the total number of cells in culture
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