Protective effect of the green tea component, l-theanine on environmental toxins-induced neuronal cell death

Parkinson’s disease is the second most common neurodegenerative disorder. It is characterized by a selective and progressive degeneration of substantia nigra (SN) dopaminergic (DA) neurons (Nagatsu and Sawada, 2007). Although, the exact mechanisms of nigral DA neuronal degeneration remains unknown, postmortem studies showed that dying cells bear the signs of apoptosis, in particular chromatin condensation, DNA fragmentation, oxidative damage, mitochondrial dysfunction, and caspase activation. Several studies demonstrated that increased oxidative stress and defective mitochondrial oxidative phosphorylation are more common in PD patients than in normal controls ( [Keeney et al., 2006] and [Schapira, 2008]). Consistent with these findings, much interest has focused on the antioxidants that may be promising therapeutics for PD.

Study from Chosun University, it has been known that green tea (Camellia sinensis) leaves contain potential antioxidant compounds such as l-theanine, caffeine, and various catechins (Chen et al., 2003). Among those chemical components in green tea, l-theanine is a natural amino acid structurally similar to glutamate and is a characteristic flavourous component of tea. Recent studies evidenced that l-theanine has neuroprotective effects on the ischemic brain damage and glutamate-induced cell death in cortical neurons ( [Egashira et al., 2004] and [Kakuda et al., 2002]). Furthermore, other studies reported that l-theanine could easily cross the blood–brain barrier, and acts in the brain ( [Yokogoshi et al., 1998a] and [Yokogoshi et al., 1998b]). On the other hand, the effect of l-theanine against the pathogenesis of PD has not been studied. Therefore, we examined the neuroprotective effects of l-theanine against rotenone- or dieldrin-induced DA neuronal damage. In this study, we found for the first time that l-theanine-mediated neuroprotection in DA neurons was involved in the attenuation of apoptotic cell death and modulation of HO-1, ERK1/2, and neurotrophic factors.

Recently, naturally occurring components such as phytochemicals have received great attention because they are perceived as safe and functional compounds to treat the neurodegenerative disorders. We paid special attention to the l-theanine contained in green tea due to its neuroprotective effects ( [Egashira et al., 2004], [Kakuda, 2002] and [Kakuda et al., 2002]). l-Theanine is a naturally occurring amino acid component found in high-grade Japanese green tea (C. sinensis). It has been known that l-theanine has multiple biological activities, such as anti-stress effects (Kimura et al., 2007), suppressive effect against the stimulatory action of caffeine (Kakuda et al., 2000) and the effect of reducing systemic blood pressure (Yokogoshi et al., 1995). l-Theanine could pass through the blood–brain barrier and transported into the brain fairly rapidly after administered orally in animal experiments ( [Yokogoshi et al., 1998a] and [Yokogoshi et al., 1998b]). Recently, it has been proposed that l-theanine has neuroprotective effects against ischemia-induced neuronal death in hippocampal CA1 region and glutamate-induced cell death in cultured rat cortical neurons ( [Kakuda, 2002], [Kakuda et al., 2000] and [Kakuda et al., 2002]). Furthermore, administration of l-theanine enhanced the concentration of dopamine in the adult brain (Yokogoshi et al., 1998a) and enhanced synthesis of neurotrophic factors and neurotransmitters during a nerve-maturing period in the infant brain (Yamada et al., 2007). However, as far as we are aware, there are no studies on the effects of l-theanine on PD. In this study, we found that l-theanine could modulate PD-related neurotoxins-induced cell death in human DA neurons. A number of possible evidences identified apoptotic cell death in the SN of PD patient ( [Anglade et al., 1997] and [Nagatsu and Sawada, 2007]). In accordance with those previous studies, our results showed the essential morphologic form of apoptosis and Caspase-3 activation when treated with rotenone or dieldrin in SH-SY5Y cells ( Fig. 2 and Fig. 3). Of interest l-theanine pretreatment significantly attenuated the chromatin condensation, nuclear fragmentation and Caspase-3 activation. From these results, it is clear that l-theanine provides some protection against the apoptotic cell death by PD-related neurotoxins.

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