theanine and Disease-Models--Animal

l-Theanine (l-THE) is a nonproteinogenic amino acid derived from green tea (Camellia sinensis), which exhibits strong antioxidant-like properties and contributes to the favourable umami taste sensation. Several studies have reported that the consumption of this amino acid has many therapeutic effects, including improvements in brain and gastrointestinal function, cancer drug therapeutic efficacies, antihypertensive effects, and improved immune function. Considering the recent Western commercialisation and popularity of green tea consumption as a nootropic agent in humans, the aims of this review were to consolidate the existing knowledge from ex vivo and in vitro animal models and attempt to highlight the applicability of l-THE towards the human clinical trials. Considering the anti-inflammatory and antioxidants effects of l-THE presented in the current review, further research must translate the existing knowledge gained from animal and cell models to exploring the potential metabolic health benefits and moderating effects on the pathogenesis of conditions such as obesity, arthritis, depression, and type 2 diabetes in human trials. This will bridge the gap in literature and provide more insights into the mechanisms driving pathologies characterised by the inflammatory response and oxidative stress.

Topics: Animals; Antihypertensive Agents; Antioxidants; Brain; Camellia sinensis; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Disease Models, Animal; Drug Evaluation, Preclinical; Glutamates; Humans; Oxidative Stress; Tea; Treatment Outcome

Theanine (n-ethylglutamic acid), a non-proteinaceous amino acid component of green and black teas, has received growing attention in recent years due to its reported effects on the central nervous system. It readily crosses the blood-brain barrier where it exerts a variety of neurophysiological and pharmacological effects. Its most well-documented effect has been its apparent anxiolytic and calming effect due to its up-regulation of inhibitory neurotransmitters and possible modulation of serotonin and dopamine in selected areas. It has also recently been shown to increase levels of brain-derived neurotrophic factor. An increasing number of studies demonstrate a neuroprotective effects following cerebral infarct and injury, although the exact molecular mechanisms remain to be fully elucidated. Theanine also elicits improvements in cognitive function including learning and memory, in human and animal studies, possibly via a decrease in NMDA-dependent CA1 long-term potentiation (LTP) and increase in NMDA-independent CA1-LTP. Furthermore, theanine administration elicits selective changes in alpha brain wave activity with concomitant increases in selective attention during the execution of mental tasks. Emerging studies also demonstrate a promising role for theanine in augmentation therapy for schizophrenia, while animal models of depression report positive improvements following theanine administration. A handful of studies are beginning to examine a putative role in attention deficit hyperactivity disorder, and theoretical extrapolations to a therapeutic role for theanine in other psychiatric disorders such as anxiety disorders, panic disorder, obsessive compulsive disorder (OCD), and bipolar disorder are discussed.

Topics: Animals; Blood-Brain Barrier; Brain-Derived Neurotrophic Factor; Cognition; Disease Models, Animal; Dopamine; Glutamates; Humans; Learning; Long-Term Potentiation; Memory; Mental Disorders; Neurodegenerative Diseases; Neuroprotective Agents; Plant Extracts; Serotonin; Synaptic Transmission; Tea

To evaluate the strength of the in vivo evidence of relationships between flavonoids and risk of stroke.. We reviewed the literature more broadly for flavonoids and stroke and conducted an evidence-based review of original publication experiments on tea or tea components on induced coronary occlusion in animal models and on the observational epidemiology on stroke and either tea or flavonoids in man. Each of the studies was evaluated by two independent reviewers. The evidence in total was compared with the Bradford Hill [1] and Stroke Therapy Academic Industry Roundtable (STAIR)(1) quality-assessment criteria [2].. The search of epidemiologic publications revealed 7 cohort studies on flavonoid intake and stroke and 7 cohort studies and 3 case control studies on tea and stroke. In studies of tea there was a consistent protective effect. However, the epidemiologic research on flavonoids and stroke was much less consistent. Eleven animal experiments were identified that examined tea or tea components and stroke relevant sequelae, eight of which reported on infarct volume. All studies demonstrated reduced infarct volumes in animals exposed either to tea extracts, theanine or tea catechins prior to or shortly after reperfusion.. Hill's criteria of causality are largely met in the case of tea and stroke. A high level of consistency across preclinical studies, of the effect of tea components as single agents effective in reducing stroke volume after middle cerebral artery occlusion, is noted in all rodent models (rat, mouse, and gerbil). Reductions in infarct volume are seen with both tea extracts consumed orally and tea components introduced intra-peritoneally. Observational epidemiology supports this finding in man for tea - the studies are consistent across countries and type of tea and the relative risks are moderately strong. That is not the case for the body of evidence on flavonoid intakes and stroke.

Topics: Animals; Catechin; Disease Models, Animal; Flavonoids; Glutamates; Humans; Mice; Neuroprotective Agents; Stroke; Tea

Topics: Animals; Cell Degranulation; Cytokines; Disease Models, Animal; Female; Hypersensitivity; Interleukin-13; Interleukin-4; Mast Cells; Mice; Mice, Inbred BALB C; Ovalbumin; Phosphatidylinositol 3-Kinases

Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons. The pathogenesis of PD includes oxidative stress, mitochondrial dysfunction, neuroinflammation, and neurotransmitter dysregulation. L-theanine is found in green tea and has antioxidant, anti-inflammatory, and neuroprotective effects with a high blood brain barrier permeability.. The objective of this study was to investigate the possible neuroprotective effect of L-theanine in lipopolysaccharide (LPS) induced motor deficits and striatal neurotoxicity in a rat model of PD.. LPS was infused at a dose of 5 μg/5 μl PBS stereotaxically into SNpc of rats. Treatment with L-theanine (50 and 100 mg/kg; po) and Sinemet (36 mg/kg; po) was given from day 7 to 21 in of LPS injected rat. On a weekly basis all behavioral parameters were assessed, and animals were sacrificed on day 22. The striatum tissue of brain was isolated for biochemicals (Nitrite, GSH, catalase, SOD, mitochondrial complexes I and IV), neuroinflammatory markers, and neurotransmitters (serotonin, dopamine, norepinephrine, GABA, and glutamate) estimations.. Results revealed that L-theanine dose-dependently and significantly reversed motor deficits, assessed through locomotor and rotarod activity. Moreover, L-theanine attenuated biochemical markers, reduced oxidative stress, and neurotransmitters dysbalance in the brain. L-theanine treatment at 100 mg/kg; po substantially reduced these pathogenic events by increasing mitochondrial activity, restoring neurotransmitter levels, and inhibiting neuroinflammation.. These data suggest that the positive effects of L-theanine on motor coordination may be mediated by the suppression of NF-κB induced by LPS. Therefore, L-theanine would have a new therapeutic potential for PD.

Topics: Animals; Disease Models, Animal; Glutamic Acid; Lipopolysaccharides; Mitochondria; Neuroinflammatory Diseases; Neuroprotective Agents; Neurotransmitter Agents; Parkinson Disease; Rats

Topics: Animals; Disease Models, Animal; Glutamates; Humans; Neuroprotective Agents; Parkinsonian Disorders; Rats; Rotenone

Topics: Animals; Antioxidants; Camellia sinensis; Dietary Supplements; Disease Models, Animal; Glutamates; Hot Temperature; Inflammation; Jejunum; Liver; Male; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Oxidative Stress; Phytotherapy; Signal Transduction; Specific Pathogen-Free Organisms

Parkinson's disease (PD) is the second most prevalent progressive neurodegenerative disease, characterized by loss of dopaminergic neurons in substantia nigra, with deficiency of dopamine in the striatum. Tramadol is safe analgesic but long-term use confirmed to elevate oxidative stress, neuroinflammation, mitochondrial dysfunction, in brain leads to motor deficits. l-Theanine is an active constituent of green tea which prevents neuronal loss, mitochondrial failure and improves dopamine, gamma-aminobutyric acid (GABA), serotonin levels and in the central nervous system (CNS) via antioxidant, anti-inflammatory, and neuromodulatory properties. In the present study, tramadol was injected intraperitoneally to Wister rats for 28 days at a dose of 50 mg/kg. l-Theanine (25, 50, and 100 mg/kg) was administered orally 3 h before tramadol administration from day 14 to day 28. Behavioral analyses including rotarod, narrow beam walk, open field, and grip strength were used to evaluate motor coordination on a weekly basis. On the day 29, all Wistar rats were sacrificed and striatum homogenates were used for biochemical (lipid peroxidation, nitrite, glutathione, glutathione peroxidase activity, superoxide dismutase, catalase, mitochondrial complex I, IV, and cyclic adenosine monophosphate), neuroinflammatory markers (tumor necrosis factor-α, interleukin-1β, and interleukin-17), and neurotransmitters (dopamine, norepinephrine, serotonin, GABA, and glutamate) analysis. Chronic tramadol treatment caused motor deficits reduced antioxidant enzymes level, increased striatal proinflammatory cytokines release, dysbalanced neurotransmitters, and reduced mitochondrial complex activity I, IV, and cAMP activity. However, l-theanine administration attenuated behavioral, biochemical, neuroinflammatory, neurotransmitters, and mitochondrial activity indicated it as a promising neuroprotective potential against degenerative changes in experimental model of PD.

Topics: Animals; Antioxidants; Corpus Striatum; Disease Models, Animal; Dopamine; gamma-Aminobutyric Acid; Glutamates; Mitochondria; Neurodegenerative Diseases; Neuroprotective Agents; Neurotransmitter Agents; Oxidative Stress; Parkinson Disease; Rats; Rats, Wistar; Serotonin; Tramadol

The present study revealed the phylactic effects of l-theanine on a DSS-induced colitis mice model. The results showed that 3% DSS treatment significantly induced intestinal damage as reflected by DAI, histopathological feature, and colon length, while l-theanine pretreatment markedly prevented these trends to exert protective effects. Meanwhile, l-theanine pretreatment decreased the levels of TNF-α, IL-1β, IL-6, iNOS, and COX2 on DSS-induced colitis. Notably, DSS inhibited the proliferation and promoted the apoptosis of intestinal epithelial cells, thereby damaging the integrity of the intestinal epithelial barrier, whereas l-theanine also played a protective role by attenuating these deteriorated effects. It was also observed that l-theanine treatment downregulated the levels of p-p65, p65, p-p53, p53, and p-AKT protein expression in acute DSS-induced colitis, which showed the protective function of l-theanine, mainly via the NF-κB signaling pathway. Furthermore, the results of lipid analysis and transcriptome analysis show that l-theanine reversed transcriptional profiles and lipid profiles of colitis models, mainly via the inflammatory reactivity-related pathway. Interestingly, the correlation analysis between transcriptional profiles and lipid profiles showed that inflammatory response-related genes were almost significantly correlated with differential lipid metabolites. In summary, l-theanine plays a protective role in DSS-induced colitis via downregulating the NF-κB signaling pathway and regulating lipid metabolism disorders.

Topics: Animals; Colitis; Colon; Dextran Sulfate; Disease Models, Animal; Glutamates; Inflammation; Lipid Metabolism; Mice; NF-kappa B; Signal Transduction

Chemotherapy is frequently used in cancer treatment; however, it may cause adverse events, which must be managed. Reactive oxygen species (ROS) have been reported to be involved in the induction of intestinal mucositis and diarrhea, which are common side effects of treatment with fluoropyrimidine 5-fluorouracil (5-FU). Our previous studies have shown that oral administration of cystine and theanine (CT) increases glutathione (GSH) production in vivo. In the present study, we hypothesized that CT might inhibit oxidative stress, including the overproduction of ROS, and attenuate 5-FU-induced mucositis and diarrhea.. We investigated the inhibitory effect of CT administration on mucositis and diarrhea, as well as its mechanism, using a mouse model of 5-FU-induced intestinal mucositis.. CT administration suppressed 5-FU-induced diarrhea and weight loss in the studied mice. After 5-FU administration, the GSH level and the GSH/GSSG ratio in the small intestine mucosal tissue decreased compared to normal control group; but CT administration improved the GSH/GSSG ratio to normal control levels. 5-FU induced ROS production in the basal region of the crypt of the small intestine mucosal tissue, which was inhibited by CT. CT did not affect the antitumor effect of 5-FU.. CT administration suppressed intestinal mucositis and diarrhea in a mouse model. This finding might be associated with the antioxidant characteristics of CT, including the improved rate of GSH redox and the reduced rate of ROS production in the small intestine mucosal tissue. CT might be a suitable candidate for the treatment of gastrointestinal mucositis associated with chemotherapy.

Topics: Animals; Cystine; Diarrhea; Disease Models, Animal; Drug Therapy, Combination; Fluorouracil; Glutamates; Humans; Intestinal Mucosa; Intestine, Small; Male; Mice; Mucositis; Oxidative Stress; Reactive Oxygen Species

Theanine and theobromine are abundantly present in tea and cocoa, respectively. This study was performed to assess the chemopreventive effects of these phytochemicals, alone or together, on dimethylhydrazine (DMH)-induced colon cancer. Thirty male Wistar rats were divided into five groups and subcutaneously injected with saline (negative control group) or 30 mg/kg DMH (the other groups) two times/week for 12 weeks. The negative and positive control animals were orally treated with drinking water, and the other groups were gavaged with theanine (400 mg/kg), theobromine (100 mg/kg), or their mixture for two weeks before and throughout the injection period. At the end of the study, the morphological and histopathological features, Ki-67 proliferation marker, and the expression of Akt/mTOR, JAK2/STAT3, MAPK/ERK, and TGF-β/Smad pathways were investigated. Theanine and theobromine, alone or together, reduced the number of cancerous and precancerous lesions, the volume of tumors, the Ki-67 immunostaining, and the expression of Akt/mTOR and JAK2/STAT3 oncogenic pathways. The simultaneous treatment was more effective in the down-regulation of Akt and mTOR compared to either theanine or theobromine alone. Theobromine administration also caused more inhibitory effects on the Ki-67 and Akt/mTOR expression than theanine. Besides, all dietary interventions increased the mRNA and protein expression of Smad2. In conclusion, theanine and theobromine, alone and in combination, inhibited tumorigenesis through down-regulation of the Akt/mTOR and JAK2/STAT3 pathways and an increment of the Smad2 tumor suppressor. The inhibition of the Akt/mTOR pathway was more pronounced by simultaneous treatment.

Topics: Animals; Anticarcinogenic Agents; Cell Proliferation; Colon; Colonic Neoplasms; Dimethylhydrazines; Disease Models, Animal; Glutamates; Janus Kinase 2; Ki-67 Antigen; Male; Proto-Oncogene Proteins c-akt; Rats, Wistar; Signal Transduction; STAT3 Transcription Factor; Theobromine; TOR Serine-Threonine Kinases

Neointimal hyperplasia is a prominent pathological phenomenon in the process of stent restenosis. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play major pathological processes involved in the development of restenosis. l-Theanine, one of the major amino acid components in green tea, has been reported to improve vascular function. Here we display the effects of l-theanine on neointima formation and the underlying mechanism. In the rat carotid-artery balloon-injury model, l-theanine greatly inhibited neointima formation and prevented VSMCs from a contractile phenotype switching to a synthetic phenotype. In vitro study showed that l-theanine significantly inhibited PDGF-BB-induced VSMC proliferation and migration, which was comparable with the effect of l-theanine on AngII-induced VSMC proliferation and migration. Western blot analysis demonstrated that l-theanine suppressed PDGF-BB and AngII-induced reduction of SMA and SM22α and increment of OPN, suggesting that l-theanine inhibited the transformation of VSMCs from contractile to the synthetic phenotype. Further experiments showed that l-theanine exhibits potential preventive effects on neointimal hyperplasia and related vascular remodeling via inhibition of phosphorylation of Elk-1 and activation of MAPK1. The present study provides the new experimental evidence that l-theanine has potential clinical application as an anti-restenosis agent for the prevention of restenosis.

Topics: Animals; Becaplermin; Carotid Artery Injuries; Cell Movement; Cell Proliferation; Cells, Cultured; Coronary Restenosis; Disease Models, Animal; ets-Domain Protein Elk-1; Glutamates; Hyperplasia; Male; Mitogen-Activated Protein Kinase 1; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Neointima; Phenotype; Rats; Rats, Sprague-Dawley; Signal Transduction; Tea

Mood disorders represent one of the most prevalent and costly psychiatric diseases worldwide. The current therapies are generally characterized by several well-known side effects which limit their prolonged use. The use of herbal medicine for the management of several psychiatric conditions is becoming more established, as it is considered a safer support to conventional pharmacotherapy. The aim of this study was to investigate the possible anxiolytic and antidepressant activity of a fixed combination of L-theanine,

Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Behavior, Animal; Cells, Cultured; Disease Models, Animal; Drug Combinations; Glutamates; Magnolia; Male; Melissa; Mice; Mood Disorders; Phytotherapy; Plant Extracts; Plants, Medicinal; Treatment Outcome

The etiology of osteoarthritis (OA) is multifactorial, with no effective disease-modifying-drugs. L-theanine has been reported to inhibit inflammatory responses in some diseases and this study aimed to investigate the effect of L-theanine on Interleukin-1(IL-1)β-stimulated chondrocytes, and in an injury-induced OA rat model. Primary chondrocytes were stimulated by IL-1β (10 ng/mL) for 24 h and then co-cultured with L-theanine for 24 h. The effects of L-theanine on IL-1β-stimulated expression of pro-inflammatory cytokines and hydrolytic enzyme were analyzed using Western blotting, quantitative polymerase chain reaction (q-PCR) and enzyme-linked immunosorbent assay (ELISA) kits. An immunofluorescence assay was used to detect nuclear factor kappa B (NF-κB) phosphorylation. OA was induced by anterior cruciate ligament transection (ACLT) surgery in rats and celecoxib was used as a positive control. OA severity was measured using the Osteoarthritis Research Society International (OARSI) grading system to describe histological changes. The results showed that L-theanine decreased the expression of pro-inflammatory mediators, including cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE-2), inducible nitric oxide synthase (iNOS), and nitric oxide (NO), both in vivo and in vitro. L-theanine treatment inhibited IL-1β-induced upregulation of matrix metalloproteinases (MMP)-3 and MMP-13, as well as inhibited NF-κB p65 activation. In vivo animal model showed that L-theanine administration (200 mg/kg) significantly alleviated OA lesions and decreased OARSI score. Our data indicated that L-theanine decreased inflammatory cytokines and protected extracellular matrix degradation through inhibition of the NF-κB pathway, and L-theanine may be considered a promising therapeutic strategy in OA prevention.

Topics: Animals; Anti-Inflammatory Agents; Chondrocytes; Cytokines; Disease Models, Animal; Extracellular Matrix; Glutamates; Inflammation Mediators; Osteoarthritis, Knee; Phosphorylation; Rats; Signal Transduction; Transcription Factor RelA; Up-Regulation

The aim of this study is to evaluate the anti-inflammatory and protective effects of L-theanine in inflammatory bowel disease (IBD) and to identify the underlying molecular mechanisms. Rats were pre-treated with L-theanine at 0, 50, 200, or 800 mg/kg/day. IBD was induced in rats using dextran sulfate sodium (DSS). Histopathological analysis suggests that L-theanine can suppress DSS-induced IBD with significant inhibition of inflammation in large and small intestinal tissues. Moreover, the 200 mg/kg/day L-theanine-treated DSS group had higher body and small intestine weights, a lower disease activity index and expression of inflammatory factors than the DSS group without pre-treatment. In RNA sequencing and tandem mass tag labeling analyses, large number of mRNAs and proteins expression level differed when compared with the DSS-induced rats with and without 200 mg/kg/day L-theanine pre-treatment. Moreover, Kyoto Encyclopedia of Genes and Genomes pathway analysis indicates the anti-inflammatory activities of L-theanine in DSS-induced IBD, with a high representation of genes in "Cholesterol metabolism" and "Retinol metabolism" pathways. Analysis of protein-protein interaction networks further indicates the involvement of these two pathways. These studies suggest that medium-dose L-theanine pre-treatment could ameliorate DSS-induced IBD through molecular mechanisms involving cholesterol and retinol metabolism.

Topics: Animals; Anti-Inflammatory Agents; Cholesterol; Dextran Sulfate; Disease Models, Animal; Dose-Response Relationship, Drug; Glutamates; Inflammation; Inflammatory Bowel Diseases; Male; Rats; Rats, Sprague-Dawley; Vitamin A

Oxaliplatin frequently causes severe peripheral neuropathy as a dose-limiting toxicity. However, this toxicity lacks a strategy for prevention. Cystine/Theanine is a supplement, which includes precursors for the biosynthesis of glutathione. In this study, we investigated the effects of Cystine/Theanine on oxaliplatin-induced peripheral neuropathy using an in vivo model. Repeated injection of oxaliplatin (4 mg/kg intraperitoneally twice a week for 2 weeks) caused mechanical allodynia, cold hyperalgesia and axonal degeneration of the sciatic nerve in rats. Mechanical allodynia and axonal degeneration, but not cold hyperalgesia, were ameliorated by daily co-administration of Cystine [200 mg/kg orally (p.o.)] and Theanine (80 mg/kg p.o.). Moreover, co-administration of Cystine and Theanine to rats significantly increased the glutathione level in the sciatic nerve compared with the oxaliplatin group. Furthermore, Cystine and Theanine did not attenuate the tumour cytotoxicity of oxaliplatin in C-26 tumour cell-bearing mice. These findings suggest that Cystine and Theanine may be beneficial for preventing oxaliplatin-induced peripheral neuropathy.

Topics: Administration, Oral; Animals; Cold Temperature; Cystine; Disease Models, Animal; Drug Therapy, Combination; Glutamates; Glutathione; Hyperalgesia; Male; Mice; Neoplasms; Oxaliplatin; PC12 Cells; Peripheral Nervous System Diseases; Rats; Rats, Sprague-Dawley; Sciatic Nerve

This study investigated the effects of L-theanine supplementation on the colonic mucosa injury in C57BL/6J male mice treated with dextran sulfate sodium (DSS)-induced colitis. Treatment with L-theanine significantly decreased the disease activity index and ameliorated the inflammation-associated pathological damage in colon length, as well as the histopathological features of DSS-induced colitis. L-Theanine administration also inhibited DSS-induced changes in the colonic tissue that included myeloperoxidase by 4.5-fold and malondialdehyde by 2.3-fold in comparison to the DSS group. In addition, GSH was increased by 85% and lipopolysaccharides level was decreased by 55% in comparison to the DSS group. Proinflammatory cytokines expression, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, at the both protein and mRNA levels were also decreased significantly. Notably, the increase in serum content of lipopolysaccharides and colonic expressions of inducible nitric oxide synthase, cyclooxygenase-2, toll like receptor (TLR)-2, TLR-4, TLR-6, and TLR-9 induced by DSS were also significantly inhibited by L-theanine administration. In addition, L-theanine also attenuated the reduction of serum contents of diamine oxidase and the production of short-chain fatty acids in the colonic tissue, and gene expression of mucosal barrier zonula occludens-1 and claudin-1 in DSS-induced colitis. Furthermore, 16S rRNA phylogenetic sequencing revealed a shift in microbial community composition induced by DSS, but no significant difference was observed following L-theanine supplementation. Overall, our findings demonstrated that L-theanine inhibits intestinal inflammation and protects against intestinal barrier disruption in mice with DSS-induced colitis. Further clinical trials should be considered to assess the effects of L-theanine supplementation on oxidative and inflammatory responses in humans.

Topics: Animals; Colitis; Dextran Sulfate; Disease Models, Animal; Glutamates; Male; Mice; Mice, Inbred C57BL; Phylogeny; RNA, Ribosomal, 16S

L-theanine, originally found in green tea, elicits various physiological effects, such as promoting relaxation, improving concentration and learning ability, and providing antianxiety-like and antidepressant-like properties. This study aims to investigate the effects of L-theanine (2 mg/kg) on monoamine levels in an animal model of depression. The effect of l-theanine on the symptoms of depression was examined through the open-field test, sucrose preference test, and forced swim test. The monoamine neurotransmitters that involve serotonin (5-HT), norepinephrine (NE), and dopamine (DA) were measured in the limbic-cortical-striatal-pallidal-thalamic (LCSPT)-circuit related brain regions, including the prefrontal cortex (PFC), nucleus accumbens (NAC), striatum (ST), amygdala, and hippocampus (HIP). L-theanine ameliorated the depressive-like behaviors in the chronic unpredictable mild stress (CUMS) rat model. In the PFC, NAC, and HIP, L-theanine administration significantly increased the levels of 5-HT, NE, and DA. In the ST, the levels of 5-HT and DA were increased after the administration of L-theanine. However, in the HIP, only the level of DA significantly changed after the treatment of L-theanine. Taken together, these results indicated that L-theanine has possibly antidepressant-like effects in the CUMS rat model, which could be mediated by the monoamine neurotransmitters in the LCSPT-circuit related brain regions.

Topics: Animals; Antidepressive Agents; Brain; Corpus Striatum; Depression; Disease Models, Animal; Dopamine; Glutamates; Hippocampus; Male; Neurotransmitter Agents; Norepinephrine; Rats; Rats, Sprague-Dawley; Serotonin; Stress, Psychological; Swimming; Tea

Tardive dyskinesia (TD) is a severe side effect of chronic neuroleptic treatment consisting of\ abnormal involuntary movements, characterized by orofacial dyskinesia (OD). Haloperidol (HAL)-\ induced OD has been widely used as an animal model to study the neuropathophysiology of human\ TD with its pathophysiology strongly associated with striatal oxidative stress. L-Theanine (LT), one\ of the major amino acid components in green tea, has potent antioxidative effects and is able to protect\ against various oxidative injuries. In this study, we examined the potential protective effects of LT\ on HAL-induced behavioral and neurochemical dysfunction in rats. HAL treatment (1 mg/kg i.p.\ for 21 days) induced significant increases (P < 0.001) in the frequency of vacuous chewing movement\ (VCM) and tongue protrusion (TP) as well as the duration of facial twitching (FT). LT treatment (100,\ 300 mg/kg orally for 35 days, starting 14 days before HAL injection) was able to prevent most of the\ HAL-induced OD. LT treatment was also able to reduce the lipid peroxidation (LPO) production, and\ enhance the antioxidation power in striatum from rats with HAL treatment. The above results indicate\ that LT has a protective role against HAL-induced OD, probably via its powerful antioxidative properties.\ Thus, LT may have a clinically relevant therapeutic effect in delaying or treating TD.

Topics: Animals; Corpus Striatum; Disease Models, Animal; Dyskinesias; Glutamates; Haloperidol; Lipid Peroxidation; Male; Rats; Rats, Wistar; Tardive Dyskinesia

Topics: Analysis of Variance; Animals; Antipsychotic Agents; Caspase 3; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Dyskinesias; Glutamates; Glutathione; Lipid Peroxidation; Male; Neurotransmitter Agents; Rats; Rats, Wistar; Reserpine; Superoxide Dismutase

Synaptic refinement improves synaptic efficiency, which provides a possibility to improve memory in Alzheimer's disease (AD). In the current study, we aimed to investigate the role of L-theanine, a natural constituent in green tea, in hippocampal synaptic transmission and to assess its potential to improve memory in transgenic AD mice. Initially, we found that L-theanine bath application facilitated hippocampal synaptic transmission and reduced paired-pulse facilitation (PPF). These effects were blocked by antagonists of N-methyl-D-aspartic acid receptors and the dopamine D1/5 receptor, and a selective protein kinase A (PKA) inhibitor. Moreover, L-theanine enhanced PKA phosphorylation via dopamine D1/5 receptor activation. L-theanine did not influence hippocampal long-term potentiation (LTP) in the slices obtained from wild-type mice, but rescued the impairment of hippocampal LTP in AD mice. Importantly, systemic application of L-theanine also improved memory and hippocampal LTP in AD mice. Our results demonstrate that L-theanine administration promotes hippocampal dopamine and noradrenaline release, and stimulates PKA phosphorylation. Moreover, the rescued hippocampal LTP in AD mice could be impaired by a PKA inhibitor. Our data reveal that L-theanine ameliorates the impairment of memory and hippocampal LTP in AD mice, likely through dopamine D1/5 receptor-PKA pathway activation. These data warrant the consideration of L-theanine as a candidate for the treatment of AD.

Topics: Alzheimer Disease; Animals; Cyclic AMP-Dependent Protein Kinases; Disease Models, Animal; Dopamine; Glutamates; Hippocampus; Long-Term Potentiation; Male; Memory; Memory Disorders; Mice, Transgenic; Neurotransmitter Agents; Nootropic Agents; Norepinephrine; Receptors, Dopamine; Receptors, N-Methyl-D-Aspartate; Synapses; Tea; Tissue Culture Techniques

Green GABA (GGABA) and Oolong GABA (OGABA) teas are relatively new varieties of tea, whose chemical composition and functional properties are largely under-studied, despite their promising health capacities. Post stroke depression (PSD) is a complication of stroke with high clinical relevance, yielding increasing mortality and morbidity rates, and a lower response to common therapies and rehabilitation.. Two chemically characterized commercial samples of GGABA and OGABA were investigated for effects on mood following oral administration using a mouse model of PSD, through common validated tests including the Despair Swimming Test and Tail Suspension Test. Moreover, the antioxidant activity of GGABA and OGABA was evaluated by determining the levels of lipid peroxidation products and the activity of antioxidant enzymes in the mouse brain in vivo.. GGABA and OGABA attenuated depressed mood by influencing behavioral parameters linked to depression. GGABA was more active than OGABA in this study, and this effect may be likely due to a higher content of polyphenolic substances and amino acids in GGABA compared to OGABA. GGABA also exerted a greater antioxidant activity.. Our data suggests that GABA tea is a promising candidate that can be used as an adjuvant in the management of PSD.

Topics: Affect; Animals; Depression; Disease Models, Animal; gamma-Aminobutyric Acid; Glutamates; Glutamic Acid; Glutamine; Lipid Peroxidation; Male; Mice; Mice, Inbred BALB C; Plant Extracts; Polyphenols; Reproducibility of Results; Stroke; Tea

Topics: Animals; Apoptosis; Brain Injuries; Cadmium; Catalase; Disease Models, Animal; Glutamates; Glutathione; Glutathione Peroxidase; In Situ Nick-End Labeling; Lipid Peroxidation; Male; Malondialdehyde; Mice; Mice, Inbred ICR; Oxidative Stress; Phosphorylation; Random Allocation; Superoxide Dismutase; tau Proteins

L-Theanine is an amino acid derivative primarily found in tea. It has been reported to promote relaxation and have neuroprotective effects. The present study was designed to investigate the role of oxidative stress and the status of antioxidant system in the management of aluminum chloride (AlCl3) induced brain toxicity in various rat brain regions and further to elucidate the potential role of L-Theanine in alleviating such negative effects. Aluminium administration significantly decreased the level of reduced glutathione and the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, Na(+)/K(+) ATPase, Ca(2+) ATPase and Mg(2+) ATPase and increased the level of lipid peroxidation and the activities of alkaline phosphatase, acid phosphatase, alanine transaminase and aspartate transaminase in all the brain regions when compared with control rats. Pre-treatment with L-Theanine at a dose of 200 mg/kg b.w. significantly increased the antioxidant status and activities of membrane bound enzymes and also decreased the level of LPO and the activities of marker enzymes, when compared with aluminium induced rats. Aluminium induction also caused histopathological changes in the cerebral cortex, cerebellum and hippocampus of rat brain which was reverted by pretreatment with L-Theanine. The present study clearly indicates the potential of L-Theanine in counteracting the damage inflicted by aluminium on rat brain regions.

Topics: Aluminum Chloride; Aluminum Compounds; Animals; Antioxidants; Cerebellum; Cerebral Cortex; Chlorides; Disease Models, Animal; Dose-Response Relationship, Drug; Glutamates; Hippocampus; Lipid Peroxidation; Male; Neurotoxicity Syndromes; Oxidative Stress; Rats

The control of inflammation is important for suppressing severe sepsis. Oral administration of cystine and theanine have been shown to suppress inflammatory responses due to invasion. Furthermore, the uptake of cystine into monocytes is promoted by exposure to lipopolysaccharide (LPS). In the present study, the effects of cystine were examined in the context of inflammatory responses.. Cystine was orally administered to mice, and the levels of interleukin (IL)-6 in the blood and spleen and the survival rates were calculated after the administration of LPS. The effects of cystine as well as neutralising anti-IL-10 antibodies on the LPS-induced production of IL-6 and IL-10 were examined in a monocyte cell line.. The oral administration of cystine reduced IL-6 levels in the blood and spleen after LPS stimulation and improved survival rates. The addition of cystine to monocytes suppressed LPS-induced IL-6 production but enhanced IL-10 production. A neutralising anti-IL-10 antibody eliminated the inhibitory effects of cystine on the LPS-induced production of IL-6.. The oral administration of cystine suppressed IL-6 production following LPS stimulation and improved survival rates in mice with LPS-induced sepsis. The enhanced production of IL-10 by monocytes may be involved in this anti-inflammatory response.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Cystine; Disease Models, Animal; Glutamates; Humans; Interleukin-10; Interleukin-6; Lipopolysaccharides; Mice; Monocytes; Sepsis; Spleen; Survival Rate

Posttraumatic stress disorder is a long-lasting psychiatric disease with the consequence of hippocampal atrophy in humans exposed to severe fatal stress. We demonstrated a positive correlation between the transient decline of 5-bromo-2'-deoxyuridine (BrdU) incorporation in the hippocampal dentate gyrus (DG) and long-lasting behavioral abnormalities in mice with traumatic stress. Here, we investigated pharmacological properties of theanine on the declined BrdU incorporation and abnormal behaviors in mice with traumatic stress. Prior daily oral administration of theanine at 50-500 mg/kg for 5 days significantly prevented the decline of BrdU incorporation, while theanine significantly prevented the decline in the DG even when administered for 5 days after stress. Consecutive daily administration of theanine significantly inhibited the prolonged immobility in mice with stress in forced swimming test seen 14 days later. Although traumatic stress significantly increased spontaneous locomotor activity over 30 min even when determined 14 days later, the increased total locomotion was significantly ameliorated following the administration of theanine at 50 mg/kg for 14 days after stress. These results suggest that theanine alleviates behavioral abnormalities together with prevention of the transient decline of BrdU incorporation in the hippocampal DG in adult mice with severe traumatic stress.

Topics: Administration, Oral; Animals; Behavior, Animal; Bromodeoxyuridine; Dentate Gyrus; Disease Models, Animal; Glutamates; Locomotion; Male; Mental Disorders; Mice, Inbred Strains; Motor Activity; Severity of Illness Index; Stress Disorders, Post-Traumatic

The effects of coadministration of melatonin and theanine (Mel/Thea) on pentylenetetrazole (PTZ)-induced seizures and brain tissue oxidative damage were investigated in ovariectomized (OVX) and sham-operated rats.. The rats were divided into the following groups: 1) sham, 2) ovariectomized (OVX), 3) sham-PTZ, 4) OVX- PTZ, 5) sham-Mel/Thea-PTZ, and 6) OVX-Mel/Thea-PTZ. Groups 1-4 received saline, while groups 5 and 6 received a combination of Mel/Thea for 6 weeks. All animals except for those in groups 1 and 2 received a single injection of PTZ.. The OVX-PTZ group had higher generalized tonic-clonic seizure (GTCS) latency compared to the sham-PTZ group. Administration of Mel/Thea increased minimal clonic seizure and GTCS latencies in both the sham-Mel/Thea-PTZ and OVX-Mel/Thea-PTZ groups compared to the controls. Additionally, PTZ exposure increased malondialdehyde levels and reduced thiol concentrations in brain tissues of both the sham-PTZ and OVX-PTZ groups. Mel/Thea pretreatment resulted in MDA reduction and thiol increase in brain tissues.. The results of this study demonstrated the antioxidant and anticonvulsant activities of Mel/Thea despite the presence or absence of ovarian hormones.

Topics: Animals; Antioxidants; Biological Availability; Brain; Central Nervous System Depressants; Disease Models, Animal; Female; Glutamates; Malondialdehyde; Melatonin; Ovariectomy; Oxidative Stress; Pentylenetetrazole; Rats; Rats, Wistar; Seizures

L-Theanine, an ethylamide derivate of glutamate found in abundance in green tea, has been shown to exert beneficial actions in animal models for several neurological disorders. We here investigated for the first time the effect of L-theanine intake on seizure susceptibility using acute pilocarpine and pentylenetetrazol (PTZ) mouse models for studying, respectively, limbic seizures or primarily generalized seizures. Moreover, we studied the effect of l-theanine intake on extracellular hippocampal and cortical glutamate and gamma-aminobutyric acid (GABA) levels, using in vivo microdialysis. Feeding mice with a 4% L-theanine solution significantly decreased their susceptibility to pilocarpine-induced seizures whereas susceptibility to PTZ-induced seizures was increased. The latter effect was linked to decreased extracellular GABA concentrations in frontal cortex.

Topics: Animals; Disease Models, Animal; GABA Agents; gamma-Aminobutyric Acid; Glutamates; Glutamic Acid; Hippocampus; Male; Mice; Mice, Inbred Strains; Microdialysis; Pentylenetetrazole; Pilocarpine; Seizures; Tea

The present work was aimed to study the protective effect of l-theanine on chronic restraint stress (CRS)-induced cognitive impairments in mice. The stress was produced by restraining the animals in well-ventilated polypropylene tubes (3.2 cm in diameter ×10.5 cm in length) for 8h once daily for 21 consecutive days. L-theanine (2 and 4 mg/kg) was administered 30 min before the animals subjected to acute immobilized stress. At week 4, mice were subjected to Morris water maze and step-through tests to measure the cognitive function followed by oxidative parameters and corticosterone as well as catecholamines (norepinephrine and dopamine) subsequently. Our results showed that the cognitive performances in CRS group were markedly deteriorated, accompanied by noticeable alterations in oxidative parameters and catecholamine levels in the hippocampus and the cerebral cortex as well as corticosterone and catecholamine levels in the serum. However, not only did l-theanine treatment exhibit a reversal of the cognitive impairments and oxidative damage induced by CRS, but also reversed the abnormal level of corticosterone in the serum as well as the abnormal levels of catecholamines in the brain and the serum. This study indicated the protective effect of l-theanine against CRS-induced cognitive impairments in mice.

Topics: Analysis of Variance; Animals; Catalase; Cognition Disorders; Corticosterone; Disease Models, Animal; Dopamine; Dose-Response Relationship, Drug; Glutamates; Glutathione; Lipid Peroxidation; Maze Learning; Mice; Norepinephrine; Oxidative Stress; Psychomotor Performance; Restraint, Physical; Stress, Psychological; Superoxide Dismutase; Time Factors

Multiple renal tubular cell adenomas and atypical tubular hyperplasia were diagnosed in 2 high-dose and 1 mid-dose female Sprague-Dawley (Crl:CD (SD)IGS BR) rats from a 90-day toxicity study of an amino acid found in green tea. The tumors were bilateral multicentric adenomas accompanied by atypical foci of renal tubular hyperplasia in both kidneys of the 3 animals. Toxic tubular changes that typically accompany renal carcinogenesis were not seen in any of the other animals of the study, suggesting rather, an underlying germline mutation of a tumor suppressor gene in these three rats. The histological appearance of these tumors and short latency was reminiscent of the spontaneous lesions reported to arise in Sprague-Dawley rats in the Nihon rat model. Nihon rats develop kidney tumors as a result of a spontaneous mutation in the rat homologue of the Birt-Hogg-Dubé gene (Bhd). Frozen samples of liver from two tumor-bearing rats were assayed for germline alterations in the Bhd gene. The entire coding region (exons 3-13) of the Bhd gene was sequenced, and a guanine (nt106G) to adenine (nt106A) polymorphism was detected resulting in a glycine to arginine (G36R) substitution in both tumor-bearing animals. In the study animals, the frequency of the A-allele (adenine) was determined to be 27% (19/70). Interestingly, rats obtained from two other sources (n = 17) only carried the nt106G-allele, consistent with the published rat sequence for this gene. Genetic fingerprinting of microsatellite loci indicated that the rats had a shared genetic background. Laser capture microdissection (LCM) of the tumor cells demonstrated a loss of heterozygosity in the Bhd gene in neoplastic cells of one of the two animals. Taken together, these data suggest that the tumors observed in these animals arose spontaneously as a result of a shared genetic susceptibility leading to the development of renal tubular neoplasms.

Topics: Adenoma; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Gene Frequency; Genetic Predisposition to Disease; Germ-Line Mutation; Glutamates; Hyperplasia; Kidney Neoplasms; Kidney Tubules; Loss of Heterozygosity; Male; Proteins; Rats; Rats, Sprague-Dawley

We investigated the involvement of gamma-aminobutyric acid(A) (GABA(A)) receptors in the neuroprotective effect of gamma-glutamylethylamide (theanine), a component of Japanese green tea, following a 4-h middle cerebral artery (MCA) occlusion in mice. Theanine (1 mg/kg) reduced the size of the cerebral infarct and alterations of NeuN, GFAP, and Iba 1 expression levels at 24 h after MCA occlusion. This neuroprotective effect of theanine was prevented by bicuculline (GABA(A)-receptor antagonist, 10 mg/kg) but not 3-mercaptopropionic acid (glutamate decarboxylase inhibitor). These results suggest that the neuroprotective effect of theanine is mediated, at least in part, by GABA(A) receptors.

Topics: Animals; Brain Ischemia; Calcium-Binding Proteins; Camellia sinensis; Disease Models, Animal; DNA-Binding Proteins; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Glutamates; Infarction, Middle Cerebral Artery; Male; Mice; Microfilament Proteins; Nerve Tissue Proteins; Neuroprotective Agents; Nuclear Proteins; Receptors, GABA-A; Tea

In the present study, we examined the neuroprotective effect of gamma-glutamylethylamide (theanine) on the ischemic brain damage in a middle cerebral artery occlusion model in mice. Theanine was injected i.p. 3 h after the occlusion or immediately before and 3 h after the occlusion. Theanine (1 mg/kg) significantly decreased the size of the cerebral infarcts 1 day after the occlusion. In contrast, theanine did not affect the cerebral blood flow, brain temperature and physiological variables (pH, pCO(2), pO(2) and hematocrit) in this model. These results suggest that theanine directly provides neuroprotection against focal cerebral ischemia and may be clinically useful for preventing cerebral infarction.

Topics: Analysis of Variance; Animals; Cerebral Infarction; Disease Models, Animal; Dose-Response Relationship, Drug; Glutamates; Infarction, Middle Cerebral Artery; Male; Mice; Neuroprotective Agents; Tetrazolium Salts