theanine and Neurodegenerative-Diseases

As the population ages, neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD) impose a heavy burden on society and families. The pathogeneses of PD and AD are complex. There are no radical cures for the diseases, and existing therapeutic agents for PD and AD have diverse side effects. Tea contains many bioactive components such as polyphenols, theanine, caffeine, and theaflavins. Some investigations of epidemiology have demonstrated that drinking tea can decrease the risk of PD and AD. Tea polyphenols can lower the morbidity of PD and AD by reducing oxidative stress and regulating signaling pathways and metal chelation. Theanine can inhibit the glutamate receptors and regulate the extracellular concentration of glutamine, presenting neuroprotective effects. Additionally, the neuroprotective mechanisms of caffeine and theaflavins may contribute to the ability to antagonize the adenosine receptor A

Topics: Animals; Antioxidants; Biflavonoids; Caffeine; Catechin; Glutamates; Herb-Drug Interactions; Humans; Neurodegenerative Diseases; Neurons; Neuroprotective Agents; Oxidative Stress; Phytochemicals; Plant Extracts; Polyphenols; Signal Transduction; Tea

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

Blood-brain barrier (BBB) impairment is related to the development of Alzheimer's disease (AD), which is dependent not only on tight junction but also on transcytosis of brain endothelial cells (BECs) in the BBB. Aging induces the decrease of ligand-specific receptor-mediated transcytosis (RMT) and the increase of non-specific caveolar transcytosis in BECs, which lead to the entry into parenchyma of neurotoxic proteins and the smaller therapeutic index in central nervous system drug delivery, further provoking neurodegenerative disease. A previous study suggests that sea-derived Antarctic krill oil (AKO) exhibits synergistic effects with land-derived nobiletin (NOB) and theanine (THE) on ameliorating memory and cognitive deficiency in SAMP8 mice. However, it is still unclear whether BBB change is involved. Hence, the effects of AKO combined with NOB and THE on aging-induced BBB impairment, including tight junction between BECs, ligand-specific RMT, and non-specific caveolar transcytosis in BECs, are investigated. The results suggest that AKO exhibits synergistic effects with NOB and THE on regulating ligand-specific RMT in BBB by inhibiting alkaline phosphatase (ALPL). The study provides a potential strategy candidate or targeted dietary patterns to prevent and treat AD by improving the BBB function.

Topics: Alkaline Phosphatase; Alzheimer Disease; Animals; Blood-Brain Barrier; Brain; Carrier Proteins; Endothelial Cells; Euphausiacea; Ligands; Mice; Neurodegenerative Diseases; Transcytosis

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