Research Database

Author: Atsushi Takeda and Haruna Tamano and Miki Suzuki and Kazuhiro Sakamoto and Naoto Oku and Hidehiko Yokogoshi

Theanine, γ-glutamylethylamide, is one of the major amino acid components in green tea. This study was undertaken to evaluate the effect of theanine intake on long-term potentiation (LTP) induction at hippocampal CA1 synapses and exposure to acute stress. Young rats were fed water containing 0.3% theanine after birth. Key findings: Serum corticosterone level was markedly decreased by theanine intake. Because this decrease can modify synaptic plasticity, the effect of theanine intake was examined focused on CA1 LTP induction. CA1 LTP induced by a 100-Hz tetanus for 1 s was almost the same extent in hippocampal slices from theanine-administered rats, whereas that induced by a 200-Hz tetanus for 1 s was significantly attenuated. 2-Amino-5-phosphonovalerate (APV), an N-methyl-d-aspartate (NMDA) receptor antagonist, significantly attenuated CA1 LTP induced by a 200-Hz tetanus in the control rats, but not in theanine-administered rats. Interestingly, APV completely blocked CA1 LTP induced by a 100-Hz tetanus in the control rats, while scarcely blocking it in theanine-administered rats. These results indicate that theanine intake reduces NMDA receptor-dependent CA1 LTP, while increasing NMDA receptor-independent CA1 LTP. Furthermore, neither 100-Hz tetanus-induced LTP nor 200-Hz tetanus-induced LTP was attenuated in theanine-administered rats after exposure to tail suspension stress, suggesting that the lack of NMDA receptor-dependent CA1 LTP by theanine intake is involved in ameliorating the attenuation of CA1 LTP after tail suspension. This study is the first to indicate that theanine intake modifies the mechanism of CA1 LTP induction.

 

 

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Proconvulsive effect of tea (Camellia sinensis) in mice 

Author: Gomes A, and Das M, and Vedasiromoni JR, and Ganguly DK

Investigations were carried out to evaluate the effect of acute and chronic administration of both black and green tea on three models of experimentally induced convulsions in mice. Tea extract (both black and green) significantly accelerated the onset of convulsion, increased the duration of convulsion and mortality in mice. Since both the extracts failed to alter the GABA level in brain, based on the earlier report that both black and green tea might act on Ca2+ channels, it can be suggested that the observed proconvulsive effect of tea is not mediated through GABA but through Ca2+ channels. 

 

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Author: Ashish Dhir

This unit describes a protocol to perform chemical kindling in mice. Kindling is a chronic animal model of epilepsy that has been extensively studied to understand the process of epileptogenesis and discover novel anti-epileptic compounds. Kindling is a phenomenon where a sub-convulsive stimulus (either chemical or electrical), if applied repetitively and intermittently, will ultimately lead to the generation of full-blown convulsions. Kindling can be induced either by (1) electrical stimulation of different brain regions (electrical kindling) or (2) using various chemical agents (chemical kindling). This unit discusses in detail the methodology to execute pentylenetetrazol (PTZ; a GABAA receptor antagonist)–induced chemical kindling in mice. PTZ is administered chronically at a sub-convulsive dose for a number of days. Seizure score is calculated after each PTZ injection. The effect of test/reference compounds can be tested by administering them either prior to the initiation of kindling (pre-kindling phase) or after animals are fully kindled (post-kindling phase). 

 

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Author: Anneleen Schallier, and Katia Vermoesen, and Ellen Loyens, and Joeri Van Liefferinge, and Yvette Michotte, and Ilse Smolders

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 vivomicrodialysis. 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.

 

 

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Author: Michael S. Ritsner, and Chanoch Miodownik, and Yael Ratner, and Tatyana Shleifer, and Maria Mar, and Leonid Pintov, and Vladimir Lerner

Objective: L-Theanine is a unique amino acid present almost exclusively in the tea plant. It possesses neuroprotective, mood-enhancing, and relaxation properties. This is a first study designed to evaluate the efficacy and tolerability of L-theanine augmentation of antipsychotic treatment of patients with chronic schizophrenia and schizoaffective disorder. Method: 60 patients with DSM-IV schizophrenia or schizoaffective disorder participated in an 8-week, double-blind, randomized, placebo-controlled study. 400 mg/d of L-theanine was added to ongoing antipsychotic treatment from February 2006 until October 2008. The outcome measures were the Positive and Negative Syndrome Scale (PANSS), the Hamilton Anxiety Rating Scale (HARS), the Cambridge Neuropsychological Test Automated Battery (CANTAB) for neurocognitive functioning, and additional measures of general functioning, side effects, and quality of life. Results: 40 patients completed the study protocol. Compared with placebo, L-theanine augmentation was associated with reduction of anxiety (P = .015; measured by the HARS scale) and positive (P = .009) and general psychopathology (P < .001) scores (measured by the PANSS 3-dimensional model). According to the 5-dimension model of psychopathology, L-theanine produced significant reductions on PANSS positive (P = .004) and activation factor (P = .006) scores compared to placebo. The effect sizes (Cohen d) for these differences ranged from modest to moderate (0.09–0.39). PANSS negative and CANTAB task scores, general functioning, side effect, and quality of life measures were not affected by L-theanine augmentation. L-Theanine was found to be a safe and well-tolerated medication. Conclusions: L-Theanine augmentation of antipsychotic therapy can ameliorate positive, activation, and anxiety symptoms in schizophrenia and schizoaffective disorder patients. Further long-term studies of L-theanine are needed to substantiate the clinically significant benefits of L-theanine augmentation.

 

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Author: Cohen-Zion M, and Ancoli-Israel S

Attention-Deficit Hyperactivity Disorder (ADHD) is the most common behavioral disorder of childhood. Multiple clinical and research reports suggest extensive sleep disturbances in children with ADHD, however, current data is contradictory. This paper reviewed 47 research studies (13 stimulant intervention and 34 naturalistic) on ADHD that were published since 1980. The main objectives of this review were to provide pediatric clinicians and researchers a clear and concise summary of published sleep data in children with ADHD, to provide a more accurate description of the current knowledge of the relationship between sleep and ADHD, and to provide current information on the effect of stimulant medication on sleep. Twenty-five of the reviewed studies used subjective reports of sleep, six were actigraphic studies, and 16 were overnight polysomnographic sleep studies (two of which also included Multiple Sleep Latency Tests). All participants were between the age of 3 and 19, and 60% were male. The results indicate high rates of parental reports of sleep disturbances in medicated and unmedicated children with ADHD, however, the majority of these findings have not been confirmed by objective sleep data. Although, agreement among objective studies is not absolute, the data suggest increased nighttime activity, reduced rapid eye movement sleep, and significant daytime somnolence in unmedicated children with ADHD when compared to controls. Data also suggest a possible increased prevalence of periodic limb movements in sleep in children with ADHD, however, little differences in sleep-disordered breathing. The limited number of studies, small and heterogeneous samples, and other methodological limitations make definite results difficult to determine. Future research will need to further clarify the relationship between sleep and ADHD and the effects of stimulants on sleep of children with ADHD.

 

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Author: Samuele Cortese and Stephen V. Faraone and Eric Konofal and Michel Lecendreux

Author: Kakuda T, and Hinoi E, and Abe A, and Nozawa A, and Ogura M, and Yoneda Y

We have previously shown that theanine (=γ-glutamylethylamide), an ingredient of green tea, has a protective effect against ischemic neuronal death in the hippocampal CA1 region of the gerbil brain without affecting ligand binding to ionotropic receptor subtypes of the neurotransmitter glutamate structurally related to theanine. The neurotransmitter pool of glutamate is thought to be fueled by the entry of the other structural analog glutamine (Gln) and subsequent cleavage by glutaminase. Although theanine did not inhibit [3H]glutamate accumulation, [3H]theanine was actively accumulated in a temperature-dependent and saturable manner in rat brain synaptosomal fractions. The accumulation of [3H]theanine was markedly inhibited by Gln in a concentration-dependent manner, whereas [3H]Gln accumulation was inhibited by theanine vice versa. Both [3H]theanine and [3H]Gln accumulations were decreased after the replacement of sodium chloride with choline chloride, along with similarly high distribution profiles in telencephalic structures. A similar equilibrium was observed within 30 min at 30°C for the accumulations of both [3H]theanine and [3H]Gln in cultured rat neocortical astroglia as well as neurons, whereas theanine inhibited [3H]Gln accumulation in a concentration-dependent manner at 0.1–10 mM. Furthermore, sustained exposure to 10 mM theanine led to a significant decrease in the level of extracellular glutamate released from cultured neurons. These results suggest that the green tea ingredient theanine would be an inhibitor of different transporters capable of transporting Gln across plasma membranes toward the modulation of the glutamate/Gln cycle required for the neurotransmitter pool of glutamate in neurons.

 

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Author: Kakuda, T. and Nozawa, A. and Sugimoto, A. and Niino, H. 

In an investigation of the mechanisms of the neuroprotective effects of theanine (gamma-glutamylethylamide) in brain ischemia, inhibition by theanine of the binding of [3H](RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), [3H]kainate, and [3H](E)-3-(2-phenyl-2-carboxyethenyl)-4,6-dichloro-1-H-indole-2-carboxylic acid (MDL 105,519) to glutamate receptors was studied in terms of its possible inhibiting effects on the three receptor subtypes (AMPA, kainate, and NMDA glycine), with rat cortical neurons. Theanine bound the three receptors, but its IC50 of theanine was 80- to 30,000-fold less than that of L-glutamic acid.

 

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Author: Hidehiko YOKOGOSHI, and Mikiko MOCHIZUKI, and Kotomi SAITOH

Following the administration of theanine, the brain tryptophan content significantly increased or tended to increase, but the contents of serotonin and 5-hydroxyindole acetic acid (5HIAA) decreased. The use of inhibitors of serotonin metabolism enable us to speculate that theanine reduced serotonin synthesis and also increased serotonin degradation in the brain.

 

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