Theanine, the Main Amino Acid in Tea, Prevents Stress-Induced Brain Atrophy by Modifying Early Stress Responses
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals and Preparation of Theanine
2.2. Housing Conditions for Stress Experiments
2.3. Magnetic Resonance (MR) Sample Preparation
2.4. MR Acquisition
2.5. MR Image Preprocessing
2.6. Minimum Deformation Template
2.7. Measurement of DNA Microarray and Principal Component Analyses
2.8. Quantitative Real-Time Reverse Transcription PCR (qRT-PCR)
2.9. Statistical Analyses
3. Results
3.1. Effect of Psychosocial Stress in SAMP10 and ddY Mice
3.2. Effect of Psychosocial Stress and Theanine Intake on Gene Expression of the Hippocampus in SAMP10
3.3. Effect of Theanine Intake on Levels of Npas4 and Lcn2 in the Brain
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
- Duman, R.S.; Aghajanian, G.K. Synaptic dysfunction in depression: Potential therapeutic targets. Science 2012, 338, 68–72. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vyas, S.; Rodrigues, A.J.; Silva, J.M.; Tronche, F.; Almeida, O.F.; Sousa, N.; Sotiropoulos, I. Chronic stress and glucocorticoids: From neuronal plasticity to neurodegeneration. Neural Plast. 2016, 2016, 6391686. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ansell, E.B.; Rando, K.; Tuit, K.; Guarnaccia, J.; Sinha, R. Cumulative adversity and smaller gray matter volume in medial prefrontal, anterior cingulate, and insula regions. Biol. Psychiatry 2012, 72, 57–64. [Google Scholar] [CrossRef] [Green Version]
- Yun, J.; Koike, H.; Ibi, D.; Toth, E.; Mizoguchi, H.; Nitta, A.; Yoneyama, M.; Ogita, K.; Yoneda, Y.; Nabeshima, T.; et al. Chronic restraint stress impairs neurogenesis and hippocampus-dependent fear memory in mice: Possible involvement of a brain-specific transcription factor Npas4. J. Neurochem. 2010, 114, 1840–1851. [Google Scholar] [CrossRef]
- Fitzsimons, C.P.; Herbert, J.; Schouten, M.; Meijer, O.C.; Lucassen, P.J.; Lightman, S. Circadian and ultradian glucocorticoid rhythmicity: Implications for the effects of glucocorticoids on neural stem cells and adult hippocampal neurogenesis. Front. Neuroendocr. 2016, 41, 44–58. [Google Scholar] [CrossRef] [Green Version]
- Hall, B.S.; Moda, R.N.; Liston, C. Glucocorticoid mechanisms of functional connectivity changes in stress-related neuropsychiatric disorders. Neurobiol. Stress 2015, 1, 174–183. [Google Scholar] [CrossRef] [Green Version]
- Liston, C.; Cichon, J.M.; Jeanneteau, F.; Jia, Z.; Chao, M.V.; Gan, W.B. Circadian glucocorticoid oscillations promote learning-dependent synapse formation and maintenance. Nat. Neurosci. 2013, 16, 698–705. [Google Scholar] [CrossRef]
- Anacker, C.; Hen, R. Adult hippocampal neurogenesis and cognitive flexibility—Linking memory and mood. Nat. Rev. Neurosci. 2017, 18, 335–346. [Google Scholar] [CrossRef]
- Gonçalves, J.T.; Schafer, S.T.; Gage, F.H. Adult neurogenesis in the hippocampus: From stem cells to behavior. Cell 2016, 167, 897–914. [Google Scholar] [CrossRef] [Green Version]
- Lieberwirth, C.; Pan, Y.; Liu, Y.; Zhang, Z.; Wang, Z. Hippocampal adult neurogenesis: Its regulation and potential role in spatial learning and memory. Brain Res. 2016, 1644, 127–140. [Google Scholar] [CrossRef]
- Hollands, C.; Tobin, M.K.; Hsu, M.; Musaraca, K.; Yu, T.S.; Mishra, R.; Kernie, S.G.; Lazarov, O. Depletion of adult neurogenesis exacerbates cognitive deficits in Alzheimer’s disease by compromising hippocampal inhibition. Mol. Neurodegener. 2017, 12, 64. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Erickson, J.D.; De Gois, S.; Varoqui, H.; Schafer, M.K.; Weihe, E. Activity-dependent regulation of vesicular glutamate and GABA transporters: A means to scale quantal size. Neurochem. Int. 2006, 48, 643–649. [Google Scholar] [CrossRef] [PubMed]
- Purkayastha, P.; Malapati, A.; Yogeeswari, P.; Sriram, D. A review on GABA/glutamate pathway for therapeutic intervention of ASD and ADHD. Curr. Med. Chem. 2015, 22, 1850–1859. [Google Scholar] [CrossRef] [PubMed]
- Martisova, E.; Solas, M.; Horrillo, I.; Ortega, J.E.; Meana, J.J.; Tordera, R.M.; Ramírez, M.J. Long lasting effects of early-life stress on glutamatergic/GABAergic circuitry in the rat hippocampus. Neuropharmacology 2012, 62, 1944–1953. [Google Scholar] [CrossRef] [PubMed]
- Pérez, M.Á.; Peñaloza-Sancho, V.; Ahumada, J.; Fuenzalida, M.; Dagnino-Subiabre, A. n-3 Polyunsaturated fatty acid supplementation restored impaired memory and GABAergic synaptic efficacy in the hippocampus of stressed rats. Nutr. Neurosci. 2017, 8, 1–14. [Google Scholar] [CrossRef] [PubMed]
- Sibbe, M.; Kulik, A. GABAergic regulation of adult hippocampal neurogenesis. Mol. Neurobiol. 2017, 54, 5497–5510. [Google Scholar] [CrossRef]
- Yun, J.; Nagai, T.; Furukawa-Hibi, Y.; Kuroda, K.; Kaibuchi, K.; Greenberg, M.E.; Yamada, K. Neuronal Per Arnt Sim (PAS) domain protein 4 (NPAS4) regulates neurite outgrowth and phosphorylation of synapsin I. J. Biol. Chem. 2013, 288, 2655–2664. [Google Scholar] [CrossRef] [Green Version]
- Unno, K.; Fujitani, K.; Takamori, N.; Takabayashi, F.; Maeda, K.; Miyazaki, H.; Tanida, N.; Iguchi, K.; Shimoi, K.; Hoshino, M. Theanine intake improves the shortened lifespan, cognitive dysfunction and behavioural depression that are induced by chronic psychosocial stress in mice. Free Radic. Res. 2011, 45, 966–974. [Google Scholar] [CrossRef]
- Unno, K.; Iguchi, K.; Tanida, N.; Fujitani, K.; Takamori, N.; Yamamoto, H.; Ishii, N.; Nagano, H.; Nagashima, T.; Hara, A.; et al. Ingestion of theanine, an amino acid in tea, suppresses psychosocial stress in mice. Exp. Physiol. 2013, 98, 290–303. [Google Scholar] [CrossRef]
- Johnson, G.A.; Ali-Sharief, A.; Badea, A.; Brandenburg, J.; Cofer, G.; Fubara, B.; Gewalt, S.; Hedlund, L.W.; Upchurch, L. High-throughput morphologic phenotyping of the mouse brain with magnetic resonance histology. Neuroimage 2007, 37, 82–89. [Google Scholar] [CrossRef] [Green Version]
- Lerch, J.P.; Gazdzinski, L.; Germann, J.; Sled, J.G.; Henkelman, R.M.; Nieman, B.J. Wanted dead or alive? The tradeoff between in-vivo versus ex-vivo MR brain imaging in the mouse. Front. Neuroinform. 2012, 6, 6. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nieman, B.J.; van Eede, M.C.; Spring, S.; Dazai, J.; Henkelman, R.M.; Lerch, J.P. MRI to assess neurological function. Curr. Protoc. Mouse Biol. 2018, 8, e44. [Google Scholar] [CrossRef] [PubMed]
- Dazai, J.; Spring, S.; Cahill, L.S.; Henkelman, R.M. Multiple-mouse neuroanatomical magnetic resonance imaging. J. Vis. Exp. 2011, 48, e2497. [Google Scholar] [CrossRef]
- de Guzman, A.E.; Wong, M.D.; Gleave, J.A.; Nieman, B.J. Variations in post-perfusion immersion fixation and storage alter MRI measurements of mouse brain morphometry. Neuroimage 2016, 142, 687–695. [Google Scholar] [CrossRef] [PubMed]
- Sasaki, K.; Sumiyoshi, A.; Nonaka, H.; Kasahara, Y.; Ikeda, K.; Hall, F.S.; Uhl, G.R.; Watanabe, M.; Kawashima, R.; Sora, I. Specific regions display altered grey matter volume in μ-opioid receptor knockout mice: MRI voxel-based morphometry. Br. J. Pharm. 2015, 172, 654–667. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sumiyoshi, A.; Riera, J.J.; Ogawa, T.; Kawashima, R. A mini-cap for simultaneous EEG and fMRI recording in rodents. Neuroimage 2011, 54, 1951–1965. [Google Scholar] [CrossRef]
- van de Ven, R.C.G.; Hogers, B.; van den Maagdenberg, A.M.J.M.; de Groot, H.J.M.; Ferrari, M.D.; Frants, R.R.; Poelmann, R.E.; van der Weerd, L.; Kiihne, S.R. T1 relaxation in in vivo mouse brain at ultra-high field. Magn. Reson. Med. 2007, 58, 390–395. [Google Scholar] [CrossRef]
- Sumiyoshi, A.; Taki, Y.; Nonaka, H.; Takeuchi, H.; Kawashima, R. Regional gray matter volume increases following 7 days of voluntary wheel running exercise: A longitudinal VBM study in rats. Neuroimage 2014, 98, 82–90. [Google Scholar] [CrossRef]
- Suzuki, H.; Sumiyoshi, A.; Taki, Y.; Matsumoto, Y.; Fukumoto, Y.; Kawashima, R.; Shimokawa, H. Voxel-based morphometry and histological analysis for evaluating hippocampal damage in a rat model of cardiopulmonary resuscitation. Neuroimage 2013, 77, 215–221. [Google Scholar] [CrossRef]
- Kale, S.C.; Lerch, J.P.; Henkelman, R.M.; Chen, X.J. Optimization of the SNR-resolution tradeoff for registration of magnetic resonance images. Hum. Brain Mapp. 2008, 29, 1147–1158. [Google Scholar] [CrossRef]
- Li, X.; Morgan, P.S.; Ashburner, J.; Smith, J.; Rorden, C. The first step for neuroimaging data analysis: DICOM to NIfTI conversion. J. Neurosci. Methods 2016, 264, 47–56. [Google Scholar] [CrossRef] [PubMed]
- Pagani, M.; Damiano, M.; Galbusera, A.; Tsaftaris, S.A.; Gozzi, A. Semi-automated registration-based anatomical labelling, voxel based morphometry and cortical thickness mapping of the mouse brain. J. Neurosci. Methods 2016, 267, 62–73. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Avants, B.B.; Epstein, C.L.; Grossman, M.; Gee, J.C. Symmetric diffeomorphic image registration with cross-correlation: Evaluating automated labeling of elderly and neurodegenerative brain. Med. Image Anal. 2008, 12, 26–41. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Klein, A.; Andersson, J.; Ardekani, B.A.; Ashburner, J.; Avants, B.; Chiang, M.-C.; Christensen, G.E.; Collins, D.L.; Gee, J.; Hellier, P.; et al. Evaluation of 14 nonlinear deformation algorithms applied to human brain MRI registration. Neuroimage 2009, 46, 786–802. [Google Scholar] [CrossRef] [Green Version]
- Johnson, G.A.; Badea, A.; Brandenburg, J.; Cofer, G.; Fubara, B.; Liu, S.; Nissanov, J. Waxholm space: An image-based reference for coordinating mouse brain research. Neuroimage 2010, 53, 365–372. [Google Scholar] [CrossRef] [Green Version]
- Cox, R.W. AFNI: Software for analysis and visualization of functional magnetic resonance neuroimages. Comput. Biomed. Res. 1996, 29, 162–173. [Google Scholar] [CrossRef]
- Tustison, N.J.; Avants, B.B.; Cook, P.A.; Zheng, Y.; Egan, A.; Yushkevich, P.A.; Gee, J.C. N4ITK: Improved N3 bias correction. IEEE Trans Med. Imaging 2010, 29, 1310–1320. [Google Scholar] [CrossRef] [Green Version]
- Avants, B.B.; Tustison, N.J.; Wu, J.; Cook, P.A.; Gee, J.C. An open source multivariate framework for n-tissue segmentation with evaluation on public data. Neuroinformatics 2011, 9, 381–400. [Google Scholar] [CrossRef] [Green Version]
- Dorr, A.E.; Lerch, J.P.; Spring, S.; Kabani, N.; Henkelman, R.M. High resolution three-dimensional brain atlas using an average magnetic resonance image of 40 adult C57Bl/6J mice. Neuroimage 2008, 42, 60–69. [Google Scholar] [CrossRef]
- Kovacević, N.; Henderson, J.T.; Chan, E.; Lifshitz, N.; Bishop, J.; Evans, A.C.; Henkelman, R.M.; Chen, X.J. A three-dimensional MRI atlas of the mouse brain with estimates of the average and variability. Cereb. Cortex 2005, 15, 639–645. [Google Scholar] [CrossRef] [Green Version]
- Sawiak, S.J.; Wood, N.I.; Williams, G.B.; Morton, A.J.; Carpenter, T.A. Voxel-based morphometry in the R6/2 transgenic mouse reveals differences between genotypes not seen with manual 2D morphometry. Neurobiol. Dis. 2009, 33, 20–27. [Google Scholar] [CrossRef]
- Kochunov, P.; Lancaster, J.L.; Thompson, P.; Woods, R.; Mazziotta, J.; Hardies, J.; Fox, P. Regional spatial normalization: Toward an optimal target. J. Comput. Assist. Tomogr. 2001, 25, 805–816. [Google Scholar] [CrossRef] [PubMed]
- Ma, Y.; Hof, P.R.; Grant, S.C.; Blackband, S.J.; Bennett, R.; Slatest, L.; McGuigan, M.D.; Benveniste, H. A three-dimensional digital atlas database of the adult C57BL/6J mouse brain by magnetic resonance microscopy. Neuroscience 2005, 135, 1203–1215. [Google Scholar] [CrossRef] [PubMed]
- Anderson, R.J.; Cook, J.J.; Delpratt, N.; Nouls, J.C.; Gu, B.; McNamara, J.O.; Avants, B.B.; Johnson, G.A.; Badea, A. Small Animal Multivariate Brain Analysis (SAMBA)—A high throughput pipeline with a validation framework. Neuroinformatics 2019, 17, 451–472. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Konishi, T. Principal component analysis for designed experiments. BMC Bioinform. 2015, 16, S7. [Google Scholar] [CrossRef] [Green Version]
- Konishi, T. Three-parameter lognormal distribution ubiquitously found in cDNA microarray data and its application to parametric data treatment. BMC Bioinform. 2004, 5, 5. [Google Scholar] [CrossRef] [Green Version]
- Konishi, T. Microarray test results should not be compensated for multiplicity of gene contents. BMC Syst. Biol. 2011, 5, S6. [Google Scholar] [CrossRef] [Green Version]
- Konishi, T. Data distribution of short oligonucleotide expression arrays and its application to the construction of a generalized intellectual framework. Stat. Appl. Genet. Mol. Biol. 2008, 7, Article25. [Google Scholar] [CrossRef]
- Ibi, D.; Takuma, K.; Koike, H.; Mizoguchi, H.; Tsuritani, K.; Kuwahara, Y.; Kamei, H.; Nagai, T.; Yoneda, Y.; Nabeshima, T.; et al. Social isolation rearing-induced impairment of the hippocampal neurogenesis is associated with deficits in spatial memory and emotion-related behaviors in juvenile mice. J. Neurochem. 2008, 105, 921–932. [Google Scholar] [CrossRef]
- Delépine, C.; Nectoux, J.; Letourneur, F.; Baud, V.; Chelly, J.; Billuart, P.; Bienvenu, T. Astrocyte transcriptome from the Mecp2(308)-truncated mouse model of Rett Syndrome. Neuromol. Med. 2015, 17, 353–363. [Google Scholar] [CrossRef]
- Choy, F.C.; Klarić, T.S.; Koblar, S.A.; Lewis, M.D. The role of the neuroprotective factor Npas4 in cerebral ischemia. Int. J. Mol. Sci. 2015, 16, 29011–29028. [Google Scholar] [CrossRef] [Green Version]
- Young, J.K.; Heinbockel, T.; Gondré-Lewis, M.C. Astrocyte fatty acid binding protein-7 is a marker for neurogenic niches in the rat hippocampus. Hippocampus 2013, 23, 1476–1483. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tirone, F.; Farioli-Vecchioli, S.; Micheli, L.; Ceccarelli, M.; Leonardi, L. Genetic control of adult neurogenesis: Interplay of differentiation, proliferation and survival modulates new neurons function, and memory circuits. Front. Cell. Neurosci. 2013, 7, 59. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mucha, M.; Skrzypiec, A.E.; Schiavon, E.; Attwood, B.K.; Kucerova, E.; Pawlak, R. Lipocalin-2 controls neuronal excitability and anxiety by regulating dendritic spine formation and maturation. Proc. Natl. Acad. Sci. USA 2011, 108, 18436–18441. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhong, J.; Jiang, L.; Huang, Z.; Zhang, H.; Cheng, C.; Liu, H.; He, J.; Wu, J.; Darwazeh, R.; Wu, Y.; et al. The long non-coding RNA Neat1 is an important mediator of the therapeutic effect of bexarotene on traumatic brain injury in mice. Brain Behav. Immun. 2017, 65, 183–194. [Google Scholar] [CrossRef]
- Shimada, A.; Tsuzuki, M.; Keino, H.; Satoh, M.; Chiba, Y.; Saitoh, Y.; Hosokawa, M. Apical vulnerability to dendritic retraction in prefrontal neurones of ageing SAMP10 mouse: A model of cerebral degeneration. Neuropathol. Appl. Neurobiol. 2006, 32, 1–14. [Google Scholar] [CrossRef]
- Shamloo, M.; Soriano, L.; von Schack, D.; Rickhag, M.; Chin, D.J.; Gonzalez-Zulueta, M.; Gido, G.; Urfer, R.; Wieloch, T.; Nikolich, K. Npas4, a novel helix-loop-helix PAS domain protein, is regulated in response to cerebral ischemia. Eur. J. Neurosci. 2006, 24, 2705–2720. [Google Scholar] [CrossRef]
- Drouet, J.B.; Peinnequin, A.; Faure, P.; Denis, J.; Fidier, N.; Maury, R.; Buguet, A.; Cespuglio, R.; Canini, F. Stress-induced hippocampus Npas4 mRNA expression relates to specific psychophysiological patterns of stress response. Brain Res. 2018, 1679, 75–83. [Google Scholar] [CrossRef]
- Coutellier, L.; Beraki, S.; Ardestani, P.M.; Saw, N.L.; Shamloo, M. Npas4: A neuronal transcription factor with a key role in social and cognitive functions relevant to developmental disorders. PLoS ONE 2012, 7, e46604. [Google Scholar] [CrossRef] [Green Version]
- Benatti, C.; Radighieri, G.; Alboni, S.; Blom, J.M.C.; Brunello, N.; Tascedda, F. Modulation of neuroplasticity-related targets following stress-induced acute escape deficit. Behav. Brain Res. 2019, 364, 140–148. [Google Scholar] [CrossRef]
- Maya-Vetencourt, J.F. Activity-dependent NPAS4 expression and the regulation of gene programs underlying plasticity in the central nervous system. Neural Plast. 2013, 2013, 683909. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Spiegel, I.; Mardinly, A.R.; Gabel, H.W.; Bazinet, J.E.; Couch, C.H.; Tzeng, C.P.; Harmin, D.A.; Greenberg, M.E. Npas4 regulates excitatory-inhibitory balance within neural circuits through cell-type-specific gene programs. Cell 2014, 157, 1216–1229. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bloodgood, B.L.; Sharma, N.; Browne, H.A.; Trepman, A.Z.; Greenberg, M.E. The activity-dependent transcription factor NPAS4 regulates domain-specific inhibition. Nature 2013, 503, 121–125. [Google Scholar] [CrossRef] [PubMed]
- Kakuda, T. Neuroprotective effects of theanine and its preventive effects on cognitive dysfunction. Pharmacol. Res. 2011, 64, 162–168. [Google Scholar] [CrossRef] [PubMed]
- Fogaça, M.V.; Duman, R.S. Cortical GABAergic dysfunction in stress and depression: New insights for therapeutic interventions. Front. Cell. Neurosci. 2019, 13, 87. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rozycka, A.; Liguz-Lecznar, M. The space where aging acts: Focus on the GABAergic synapse. Aging Cell 2017, 16, 634–643. [Google Scholar] [CrossRef] [PubMed]
- Sun, X.; Lin, Y. Npas4: Linking neuronal activity to memory. Trends Neurosci. 2016, 39, 264–275. [Google Scholar] [CrossRef] [Green Version]
- Zullo, J.M.; Drake, D.; Aron, L.; O’Hern, P.; Dhamne, S.C.; Davidsohn, N.; Mao, C.-A.; Klein, W.H.; Rotenberg, A.; Bennett, D.A.; et al. Regulation of lifespan by neural excitation and REST. Nature 2019, 574, 359–364. [Google Scholar] [CrossRef]
- Jha, M.K.; Lee, S.; Park, D.H.; Kook, H.; Park, K.G.; Lee, I.K.; Suk, K. Diverse functional roles of lipocalin-2 in the central nervous system. Neurosci. Biobehav. Rev. 2015, 49, 135–156. [Google Scholar] [CrossRef]
- Suk, K. Lipocalin-2 as a therapeutic target for brain injury: An astrocentric perspective. Prog. Neurobiol. 2016, 144, 158–172. [Google Scholar] [CrossRef]
- Lee, S.; Lee, W.H.; Lee, M.S.; Mori, K.; Suk, K. Regulation by lipocalin-2 of neuronal cell death, migration, and morphology. J. Neurosci. Res. 2012, 90, 540–550. [Google Scholar] [CrossRef] [PubMed]
- Flower, D.R.; North, A.C.; Sansom, C.E. The lipocalin protein family: Structural and sequence overview. Biochim. Biophys. Acta 2000, 1482, 9–24. [Google Scholar] [CrossRef]
- Kim, H.J.; Tsao, J.W.; Stanfill, A.G. The current state of biomarkers of mild traumatic brain injury. JCI Insight 2018, 3, 97105. [Google Scholar] [CrossRef] [PubMed]
- Naudé, P.J.; Nyakas, C.; Eiden, L.E.; Ait-Ali, D.; van der Heide, R.; Engelborghs, S.; Luiten, P.G.; De Deyn, P.P.; den Boer, J.A.; Eisel, U.L. Lipocalin 2: Novel component of proinflammatory signaling in Alzheimer’s disease. FASEB J. 2012, 26, 2811–2823. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Matsumata, M.; Sakayori, N.; Maekawa, M.; Owada, Y.; Yoshikawa, T.; Osumi, N. The effects of Fabp7 and Fabp5 on postnatal hippocampal neurogenesis in the mouse. Stem Cells 2012, 30, 1532–1543. [Google Scholar] [CrossRef] [PubMed]
PC2 | Biological Process | Selected | Total | p-Value |
---|---|---|---|---|
Positive | Oxidation-reduction process | 40 | 854 | 0 |
Transport | 40 | 2011 | 4.22 × 10 −7 | |
Regulation of transcription, DNA-templated | 31 | 2447 | 0.0140 | |
Multicellular organismal development | 20 | 1074 | 0.0008 | |
Cell adhesion | 16 | 530 | 1.32 × 10 −5 | |
Apoptotic process | 16 | 607 | 6.54 × 10 −5 | |
Lipid metabolic process | 14 | 472 | 5.48 × 10 −5 | |
Ion transport | 13 | 633 | 0.0029 | |
Glucose metabolic process | 13 | 79 | 3.03 × 10 −13 | |
Regulation of translation | 13 | 140 | 3.28 × 10 −10 | |
Negative | Regulation of transcription, DNA-templated | 76 | 2447 | 0.0002 |
Transcription, DNA-templated | 70 | 1983 | 9.61 × 10 −6 | |
Signal transduction | 69 | 2582 | 0.0152 | |
Transport | 69 | 2011 | 2.70 × 10 −5 | |
Metabolic process | 45 | 1595 | 0.0205 | |
Multicellular organismal development | 42 | 1074 | 7.15 × 10 −5 | |
Cell adhesion | 37 | 530 | 2.57 × 10 −10 | |
Phosphorylation | 37 | 737 | 9.82 × 10 −7 | |
Protein phosphorylation | 37 | 667 | 9.30 × 10 −8 | |
Positive regulation of transcription from RNA Polymerase II promoter | 33 | 899 | 0.0012 |
Symbol | Full Name | ΔZ | p | |
---|---|---|---|---|
Up-regulated | Npas4 | Neuronal PAS domain protein 4 | 0.3210 | 8.32 × 10 −21 |
Fabp7 | Fatty acid binding protein 7, brain | 0.0926 | 1.25 × 10 −31 | |
n-R5s70 | Nuclear encoded rRNA 5S 70 | 0.2585 | 0.0028 | |
Opalin | Oligodendrocytic myelin paranodal and inner loop protein | 0.2031 | 2.67 × 10 −24 | |
Olfr1474 | Olfactory receptor 1474 | 0.3071 | 0.0011 | |
Igkv14–130 | Immunoglobulin kappa variable 14–130 | 0.2886 | 0.0027 | |
Vmn2r78 | Vomeronasal 2, receptor 78 | 0.2541 | 0.0016 | |
Triml2 | Tripartite motif family-like 2 | 0.2697 | 0.0032 | |
Btg2 | B cell translocation gene 2, anti-proliferative | 0.2027 | 1.86 × 10 −11 | |
Igkv18–36 | Immunoglobulin kappa chain variable 18–36 | 0.2167 | 0.0034 | |
Down-regulated | Mela | Melanoma antigen | −0.6668 | 6.16 × 10 −64 |
Ly6a | Lymphocyte antigen 6 complex, locus A | −0.4346 | 1.01 × 10 −8 | |
Lcn2 | Lipocalin 2 | −0.3125 | 2.37 × 10 −7 | |
Prg4 | Proteoglycan 4 | −0.2707 | 4.82 × 10 −7 | |
Neat1 | Nuclear paraspeckle assembly transcript 1 | −0.3590 | 1.41 × 10 −18 | |
C1qb | Complement component 1, q subcomponent, beta polypeptide | −0.2347 | 1.54 × 10 −17 | |
Vwf | Von Willebrand factor homolog | −0.2057 | 7.46 × 10 −21 | |
C1qc | Complement component 1, q subcomponent, C chain | −0.2948 | 4.38 × 10 −9 | |
Hbb-b2 | Hemoglobin, beta adult minor chain | −0.2340 | 1.30 × 10 −8 | |
Etnppl | Ethanolamine phosphate phospholyase | −0.2038 | 1.84 × 10 −7 |
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Unno, K.; Sumiyoshi, A.; Konishi, T.; Hayashi, M.; Taguchi, K.; Muguruma, Y.; Inoue, K.; Iguchi, K.; Nonaka, H.; Kawashima, R.; et al. Theanine, the Main Amino Acid in Tea, Prevents Stress-Induced Brain Atrophy by Modifying Early Stress Responses. Nutrients 2020, 12, 174. https://doi.org/10.3390/nu12010174
Unno K, Sumiyoshi A, Konishi T, Hayashi M, Taguchi K, Muguruma Y, Inoue K, Iguchi K, Nonaka H, Kawashima R, et al. Theanine, the Main Amino Acid in Tea, Prevents Stress-Induced Brain Atrophy by Modifying Early Stress Responses. Nutrients. 2020; 12(1):174. https://doi.org/10.3390/nu12010174
Chicago/Turabian StyleUnno, Keiko, Akira Sumiyoshi, Tomokazu Konishi, Michiko Hayashi, Kyoko Taguchi, Yoshio Muguruma, Koichi Inoue, Kazuaki Iguchi, Hiroi Nonaka, Ryuta Kawashima, and et al. 2020. "Theanine, the Main Amino Acid in Tea, Prevents Stress-Induced Brain Atrophy by Modifying Early Stress Responses" Nutrients 12, no. 1: 174. https://doi.org/10.3390/nu12010174
APA StyleUnno, K., Sumiyoshi, A., Konishi, T., Hayashi, M., Taguchi, K., Muguruma, Y., Inoue, K., Iguchi, K., Nonaka, H., Kawashima, R., Hasegawa-Ishii, S., Shimada, A., & Nakamura, Y. (2020). Theanine, the Main Amino Acid in Tea, Prevents Stress-Induced Brain Atrophy by Modifying Early Stress Responses. Nutrients, 12(1), 174. https://doi.org/10.3390/nu12010174