L-theanine inhibits mammalian target of rapamycin-p70S6K pathway-mediated neuroexcitation induced by N-methyl-D-aspartate
Year: 2025
Type: article
Abstract: Background The phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathways are important for cell survival, proliferation, and migration. Therefore, mTOR signaling via Ca 2+ influx may influence nervous system function and cell viability. L-theanine is a naturally occurring component of green tea, and its structure is similar to that of L-glutamine. It is also known that neurotoxicity caused by excessive Ca 2+ influx is protected by L-theanine pretreatment. Hence, this study investigated whether L-theanine, which can potentially suppress nervous system function, reduces c-Fos expression associated with N-methyl-D-aspartate (NMDA)-type administration. Methods We used adult ddY mice to measure amino acid content by HPLC. We also used immunoblot assays to detect various protein expressions in the mouse hippocampus. Results It was determined that the correlation coefficient between NMDA-induced c-Fos protein expression and S6 ribosomal protein phosphorylation in the untreated L-theanine group was r = 0.19. In contrast, the correlation coefficient between NMDA-induced c-Fos expression and S6 phosphorylation in the L-theanine-treated group was r = 0.94. Moreover, the increase in 70-kDa ribosomal protein S6 kinase (p70S6K) phosphorylation by NMDA treatment was abolished by concomitant L-theanine treatment. In contrast, 90-kDa ribosomal protein S6 kinase (p90RSK) phosphorylation increased upon NMDA treatment, which was not reversed by the L-theanine combination. Conclusion The lack of a correlation between c-Fos and S6 phosphorylation is due to a complex signaling induce by NMDA. It has been suggested that the mTOR-p70S6K pathway may mediate the "toxic and troublesome" aspects of NMDA-induced excitation and that L-theanine may be able to cancel this. L-theanine may reduce neuronal excitation and exert sedative and neuroprotective effects.
Source: Current Molecular Pharmacology
Institution: Setsunan University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Awards: Exploring new molecular to depression vulnerability formation in striatum, Elucidation of key genes for the progression of amyotrophic lateral sclerosis - aiming for gene therapy -, Demonstration of the neurodegeneration prevention effect of an orally administered neuron-specific potassium excretion promoter.
OpenAlex ID: W4413114679