dizocilpine-maleate and theanine

L-Theanine (N-ethyl-L: -glutamine) is an amino acid uniquely found in green tea and historically considered to be a relaxing agent. It is a glutamate derivative and has an affinity for glutamatergic receptors. However, its psychotropic effects remain unclear.. To elucidate effects of L: -theanine on psychiatric disease-related behaviors in mice and its molecular basis focusing on brain-derived neurotrophic factor (BDNF) and N-methyl-D: -aspartate (NMDA) receptor.. We examined the effects of L: -theanine on behaviors in mice by using the open-field test (OFT), forced swim test (FST), elevated plus-maze test (EPMT), and prepulse inhibition (PPI) of acoustic startle. By western blot analysis, we looked at the effect of L: -theanine on the expression of BDNF and related proteins in the hippocampus and cerebral cortex. To determine whether L: -theanine has agonistic action on the NMDA receptor, we performed Fluo-3 intracellular Ca(2+) imaging in cultured cortical neurons.. Single administration of L: -theanine significantly attenuated MK-801-induced deficits in PPI. Subchronic administration (3-week duration) of L: -theanine significantly reduced immobility time in the FST and improved baseline PPI. Western blotting analysis showed increased expression of BDNF protein in the hippocampus after subchronic administration of L: -theanine. In cultured cortical neurons, L: -theanine significantly increased the intracellular Ca(2+) concentration, and this increase was suppressed by competitive and non-competitive NMDA receptor antagonists (AP-5 and MK-801, respectively).. Our results suggest that L: -theanine has antipsychotic-like and possibly antidepressant-like effects. It exerts these effects, at least in part, through induction of BDNF in the hippocampus and the agonistic action of L: -theanine on the NMDA receptor.

Topics: Animals; Behavior, Animal; Brain-Derived Neurotrophic Factor; Calcium; Dizocilpine Maleate; Gene Expression Regulation; Glutamates; Hippocampus; Male; Maze Learning; Mice; Mice, Inbred C57BL; Receptors, N-Methyl-D-Aspartate; Reflex, Startle

As a natural analogue of glutamate, l-theanine is the unique amino acid derivative in green tea. Although its underlining mechanisms are not yet clear, it has been suggested that l-theanine treatment may prove beneficial to patients with neurodegenerative diseases. In this study, we investigated the neuroprotective effect and its mechanism of l-theanine in an in vitro model of Alzheimer's disease by using the human APP (Swedish mutation) transgenic SH-SY5Y cell. Amyloid beta (Abeta) neurotoxicity was triggered by l-glutamate in this cell line. Additionally, l-theanine significantly attenuated l-glutamate-induced apoptosis at similar levels to those seen with the NMDA receptor inhibitor MK-801 in the stably expressing APP Swedish mutation SH-SY5Y cells which over-generated Abeta. Meanwhile, the activation of c-Jun N-terminal kinase and caspase-3 induced by l-glutamate was suppressed by l-theanine. We also found that cells treated with l-theanine showed decreased production of nitric oxide resulting from the down-regulated protein levels of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS). These results indicate that the inhibition of the NMDA subtype of glutamate receptors and its related pathways is the crucial point of the neuroprotective effect of l-theanine in the cell model. Thus, our present study supports the notion that l-theanine may provide effective prophylaxis and treatment for Alzheimer's disease.

Topics: Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Apoptosis; Calcium; Caspase 3; Cell Line, Tumor; Cell Survival; Dizocilpine Maleate; Glutamates; Glutamic Acid; Humans; JNK Mitogen-Activated Protein Kinases; Mutation; Neurons; Neuroprotective Agents; Nitric Oxide; Nitric Oxide Synthase; omega-N-Methylarginine; Peptide Fragments; Phosphorylation; Receptors, N-Methyl-D-Aspartate; Signal Transduction; Transgenes

Theanine, r-glutamylethylamide, is one of the major components of amino acids in Japanese green tea. Effect of theanine on brain amino acids and monoamines, and the striatal release of dopamine (DA) was investigated. Determination of amino acids in the brain after the intragastric administration of theanine showed that theanine was incorporated into brain through blood-brain barrier via leucine-preferring transport system. The concentrations of norepinephrine, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole acetic acid (5HIAA) in the brain regions were unaffected by the theanine administration except in striatum. Theanine administration caused significant increases in serotonin and/or DA concentrations in the brain, especially in striatum, hypothalamus and hippocampus. Direct administration of theanine into brain striatum by microinjection caused a significant increase of DA release in a dose-dependent manner. Microdialysis of brain with calcium-free Ringer buffer attenuated the theanine-induced DA release. Pretreatment with the Ringer buffer containing an antagonist of non-NMDA (N-methyl-D-aspartate) glutamate receptor, MK-801, for 1 hr did not change the significant increase of DA release induced by theanine. However, in the case of pretreatment with AP-5, (+/-)-2-amino-5-phosphonopentanoic acid; antagonist of NMDA glutamate receptor, the theanine-induced DA release from striatum was significantly inhibited. These results suggest that theanine might affect the metabolism and/or the release of some neurotransmitters in the brain, such as DA.

Topics: 2-Amino-5-phosphonovalerate; 3,4-Dihydroxyphenylacetic Acid; Alanine; Amino Acids; Animals; Biogenic Monoamines; Brain; Carrier Proteins; Consciousness; Corpus Striatum; Dizocilpine Maleate; Dopamine; Glutamates; Hydroxyindoleacetic Acid; Kinetics; Leucine; Male; Norepinephrine; Organ Specificity; Rats; Rats, Wistar; Stereoisomerism; Tea