Theanine, r-glutamylethylamide, increases neurotransmission concentrations and neurotrophin mRNA levels in the brain during lactation
Introduction
Recently, many studies have shown that green tea and various green tea leaf components such as catechins, caffeine and γ-aminobutyric acid (GABA) have physiological and pharmacological actions. Especially, GABA is known as an inhibitory neurotransmitter present almost exclusively in the central nerve system (CNS) (Brambilla et al., 2003), and GABAergic dysfunction causes mood disorders or neurological disorders such as seizures (Wong et al., 2003). Theanine is also a major amino acid component in green tea, but little is known about its effect on organism. Previously, we showed theanine concentrations in various rat tissues by intragastrical administration of theanine (Terashima et al., 1999). Theanine was detected in the serum, liver and brain. The concentrations were time- and dose-dependent. Further, we suggested that theanine might be degraded via glutamic acid. Its structure is similar to glutamic acid or GABA. Using an in vivo brain microdialysis method, we showed that direct administration of theanine into the rat striatal brain enhanced the release of dopamine (Yokogoshi et al., 1998a). In addition, some other researchers suggested that theanine altered some neurotransmitter concentrations in the rat brain. Intraperitoneal administration of theanine inhibited the convulsive action of caffeine, and increased intracerebral levels of GABA in mice (Kimura and Murata, 1971). Theanine decreased norepinephrine levels in the rat brain, and depressed caffeine-increased levels of serotonin and 5-hydroxyindoleacetic acid in rats (Kimura and Murata, 1986). Other reports showed that theanine decreased the serotonin concentration and increased the tryptophan concentration in the rat brain (Yokogoshi et al., 1998b). In addition, theanine administrated into the lateral ventricle prevented ischemia-induced neuronal death in hippocampal CA1 region in a dose-dependent manner, and a previous report suggested that the neuroprotective effect of theanine is exhibited via glutamate receptors, with theanine acting as a glutamate receptor antagonist (Kakuda et al., 2000, Kakuda, 2002). These results suggest that theanine modulates brain functions such as learning, memory and emotions. Furthermore, in a recent report, we suggested that theanine enhanced inhibitory neurotransmission (Yamada et al., 2005). Theanine perfusion promoted glycine release in the rat striatum brain. Glycine is major inhibitory neurotransmitter, as well as GABA, and performs many important functions in the brain (Legendre, 2001, Lopez-Corcuera et al., 2001). We suggest that theanine mediates GABA neurotransmission (data is not published). On the other hand, it was shown that inhibitory neurotransmission requires postnatal central nerve system maturation (Ganguly et al., 2001). The purpose of this study was to investigate the effects of theanine on the central nerve systems in postnatal infant rats.
It is known that excitatory neurotransmission is required to build the nerve network between neurons and many other functions in the CNS. Usually, an excitatory neurotransmitter, such as glutamate, evokes excitation of neurons in the mature mammalian. However, in the infant, GABA works like an excitatory neurotransmitter, because chloride concentration in the neuron is kept higher than outside (Ganguly et al., 2001). Hence, when GABA receptors open, chloride flows out from the neuron and evokes excitatory neurotransmission. We hypothesized that if theanine promotes inhibitory neurotransmission in neonatal infants, it promotes nerve network maturation, along with maturation of other structures in the CNS.
In addition, some neurotrophic factors work to promote growth of neurons during the neuronal development state. Some main factors are nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). These mRNA levels increase by excitatory neurotransmission (Wu et al., 2004) and especially, NGF mRNA level increases during neuronal maturation in rats. At 3 weeks postnatally, it is at the adult level (Whittemore et al., 1986) This was observed by GABA neurotransmission during early neuronal development (Obrietan and van den Pol , 1995).
In this study, we measured the amino acids relationship to neuronal maturation and neurotransmitter concentrations, and we measured neurotrophic factor mRNA level in 1-week, 2-week and 3-week-old rats, respectively. In addition, we plan to examine the effect of theanine on neuronal development in neonates.
Section snippets
Animals for measuring amino acid concentrations in mother's milk
Sixteen pregnant Wistar rats (SLC, Hamamatsu, Japan) were kept in individual wire cages in a temperature- and humidity-controlled room (24 °C and 55% relative humidity) under regular lightning conditions (12 h light:dark cycle). These rats were given a stock diet (CE-2: CLEA JAPAN, Tokyo, Japan) and tap water ad libitum. After the confinement, the condition and foods did not change. This experiment was carried out in accordance with Guidelines for the care and use of laboratory animals of the
Amino acid concentrations in mother's milk
The quantity of obtained milk was not different between the group administered theanine and the control group. Theanine was detected in the theanine-administrated dams' milk. Glycine, taurine and glutamate concentrations were increased significantly (Table 1).
Amino acid concentrations in serum
Theanine was fed to dams after the confinement. The quantity of water intake was not different between the two groups. The rate of body weight gain of dams and infants was not different between the two groups (Fig. 1, Fig. 2).
Theanine was
Discussion
Excitatory neurotransmission is needed for the nerve growth. Glutamate works as an excitatory neurotransmitter. Glutamate stimulates open cation channel receptors and allows activation of neuron function. These changes enhance synthesis of NGF and BDNF, and these enhance synthesis of functional proteins of the nervous systems. These results cause dendrite elongation and new connections of neuron networks (Lujan et al., 2005, Tang et al., 1999, Brian and Meldrum, 2000). Recent studies have shown
Acknowledgements
This work was supported in part by grants for scientific research from Shizuoka Prefecture, and the 21st century COE program from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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