Essential Role of Keap1-Nrf2 Signaling in Mood Disorders: Overview and Future Perspective

Hashimoto, Kenji

doi:10.3389/fphar.2018.01182

Cited by 98Tryptophan and brain disordersTreatment of Major DepressionGenomics, phytochemicals, and oxidative stress

Essential Role of Keap1-Nrf2 Signaling in Mood Disorders: Overview and Future Perspective

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Hashimoto, Kenji·2018·Frontiers in Pharmacology

DOI 10.3389/fphar.2018.01182PMC PMC6198170

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Abstract

Depression is one of the most common mood disorders with a high rate of relapse. Accumulating evidence suggests that the transcription factor Kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated protein 1 (Keap1)- Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) system plays a key role in inflammation which is involved in depression. Preclinical studies demonstrated that the protein expressions of Keap1 and Nrf2 in the prefrontal cortex (PFC), CA3 and dentate gyrus (DG) of hippocampus in mice with depression-like phenotype were lower than control mice. In the learned helplessness paradigm, the protein levels of Keap1 and Nrf2 in the PFC and DG of hippocampus from rats with depression-like phenotype were also lower than control and resilient rats. Furthermore, rodents with depression-like phenotype have higher levels of pro-inflammatory cytokines. Interestingly, Nrf2 knock-out (KO) mice exhibit depression-like phenotype, and higher serum levels of pro-inflammatory cytokines compared with wild-type mice. Furthermore, Nrf2 KO mice have lower expression of brain-derived neurotrophic factor (BDNF) in the PFC, and CA3 and DG of hippocampus compared to wild-type mice. 7,8-Dihydroxyflavone, a TrkB agonist, showed antidepressant effects in Nrf2 KO mice, by stimulating BDNF-TrkB in the PFC, CA3 and DG. Pretreatment with sulforaphane, a naturally occurring Nrf2 activator, prevented depression-like phenotype in mice after inflammation or chronic social defeat stress. Interestingly, dietary intake of 0.1% glucoraphanin (a precursor of sulforaphane) containing food during juvenile and adolescent stages of mice could prevent depression-like phenotype in adulthood after chronic social defeat stress. Moreover, the protein expressions of Keap1 and Nrf2 in the parietal cortex from major depressive disorder and bipolar disorder were lower than controls. These findings suggest that Keap1-Nrf2 system plays a key role in the stress resilience which is involved in the pathophysiology of mood disorders. It is, therefore, possible that dietary intake of cruciferous vegetables including glucoraphanin (or SFN) may prevent or minimize relapse from remission, induced by stress and/or inflammation in depressed patients. In the review, the author would like to discuss the role of Keap1-Nrf2 system in mood disorders.

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Increasing preclinical and clinical evidence suggests that higher levels of oxidative stress, alterations in the Keap1-Nrf2 pathway, and Nrf2-associated inflammation are involved in the pathogenesis of psychiatric disorders.
“however, increasing preclinical and clinical evidence suggests that higher levels of oxidative stress, alterations in the Keap1-Nrf2 pathway, and Nrf2-associated inflammation are involved in the pathogenesis of these psychiatric disorders [128,129,130,131,132].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [132]

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Utilization of Dimethyl Fumarate and Related Molecules for Treatment of Multiple Sclerosis, Cancer, and Other Diseases
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Regional differences in the expression of brain-derived neurotrophic factor (BDNF) pro-peptide, proBDNF and preproBDNF in the brain confer stress resilience
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Keap1-Nrf2 signaling pathway confers resilience versus susceptibility to inescapable electric stress
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Sulforaphane from Broccoli Reduces Symptoms of Autism: A Follow-up Case Series from a Randomized Double-blind Study
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Peripheral interleukin-6 promotes resilience versus susceptibility to inescapable electric stress
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Effects of amycenone on serum levels of tumor necrosis factor-α, interleukin-10, and depression-like behavior in mice after lipopolysaccharide administration
Yao, W., Zhang, J.-C., Dong, C., Zhuang, C., Hirota, S., Inanaga, K., & Hashimoto, K. (2015) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2015.06.012 · Cited by 52 · see citing works
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Dietary glucoraphanin prevents the onset of psychosis in the adult offspring after maternal immune activation
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Dl-3-n-Butylphthalide improves lipopolysaccharide-induced depressive-like behavior in rats: involvement of Nrf2 and NF-κB pathways
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Adolescent Brain Vulnerability and Psychopathology Through the Generations: Role of Diet and Dopamine
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Role of Keap1-Nrf2 Signaling in Anhedonia Symptoms in a Rat Model of Chronic Neuropathic Pain: Improvement With Sulforaphane
Li, S., Yang, C., Fang, X., Zhan, G., Huang, N., Gao, J., Xu, H., Hashimoto, K., & Luo, A. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00887 · Cited by 37 · see citing works
Antidepressant effects of TBE-31 and MCE-1, the novel Nrf2 activators, in an inflammation model of depression
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Novel Tricyclic Compounds Having Acetylene Groups at C-8a and Cyano Enones in Rings A and C: Highly Potent Anti-inflammatory and Cytoprotective Agents
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Insights into the potential antidepressant mechanisms of cilostazol in chronically restraint rats: impact on the Nrf2 pathway
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Pharmacokinetics and pharmacodynamics of orally administered acetylenic tricyclic bis (cyanoenone), a highly potent Nrf2 activator with a reversible covalent mode of action
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Structure‐based discovery of low molecular weight compounds that stimulate neurite outgrowth and substitute for nerve growth factor
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Astragaloside IV attenuates lead acetate-induced inhibition of neurite outgrowth through activation of Akt-dependent Nrf2 pathway in vitro
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ω-3 and major depression: a review
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Recent Advances in Nutrition for the Treatment of Depressive Disorder
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Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease
Ngo, V., & Duennwald, M. L. (2022) · Antioxidants · doi:10.3390/antiox11122345 · Cited by 1,130 · see citing works
Melatonin Attenuates LPS-Induced Acute Depressive-Like Behaviors and Microglial NLRP3 Inflammasome Activation Through the SIRT1/Nrf2 Pathway
Arioz, B. I., Tastan, B., Tarakcioglu, E., Tufekci, K. U., Olcum, M., Ersoy, N., Bagriyanik, A., Genc, K., & Genc, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01511 · Cited by 516 · see citing works
Nrf2: An all-rounder in depression
Zuo, C., Cao, H., Song, Y., Gu, Z., Huang, Y., Yang, Y., Miao, J., Zhu, L., Chen, J., Jiang, Y., et al. (2022) · Redox Biology · doi:10.1016/j.redox.2022.102522 · Cited by 138 · see citing works
The role of natural products in revealing NRF2 function
Zhang, D. D., & Chapman, E. (2020) · Natural Product Reports · doi:10.1039/c9np00061e · Cited by 120 · see citing works
Activation of BDNF by transcription factor Nrf2 contributes to antidepressant-like actions in rodents
Yao, W., Lin, S., Su, J. Y., Cao, Q., Chen, Y., Chen, J., Zhang, Z., Hashimoto, K., Qi, Q., & Zhang, J. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01261-6 · Cited by 106 · see citing works
Role of Soluble Epoxide Hydrolase in Metabolism of PUFAs in Psychiatric and Neurological Disorders
Hashimoto, K. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00036 · Cited by 95 · see citing works
Nrf2 activator, sulforaphane ameliorates autism-like symptoms through suppression of Th17 related signaling and rectification of oxidant-antioxidant imbalance in periphery and brain of BTBR T+tf/J mice
Nadeem, A., Ahmad, S. F., Al-Harbi, N. O., Attia, S. M., Bakheet, S. A., Ibrahim, K. E., Alqahtani, F., & Alqinyah, M. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.02.031 · Cited by 90 · see citing works
Escitalopram Targets Oxidative Stress, Caspase-3, BDNF and MeCP2 in the Hippocampus and Frontal Cortex of a Rat Model of Depression Induced by Chronic Unpredictable Mild Stress.
Dionisie, V., Ciobanu, A. M., Toma, V. A., Manea, M. C., Baldea, I., Olteanu, D., Sevastre-Berghian, A., Clichici, S., Manea, M., Riga, S., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147483 · Cited by 78 · see citing works
Quercetin reverses chronic unpredictable mild stress-induced depression-like behavior in vivo by involving nuclear factor-E2-related factor 2
Guan, Y., Wang, J., Wu, X., Song, L., Wang, Y., Gong, M., & Li, B. (2021) · Brain Research · doi:10.1016/j.brainres.2021.147661 · Cited by 57 · see citing works
Nrf2 regulates the arginase 1+ microglia phenotype through the initiation of TREM2 transcription, ameliorating depression-like behavior in mice
He, L., Zheng, Y., Huang, L., Ye, J., Ye, Y., Luo, H., Chen, X., Yao, W., Chen, J., & Zhang, J. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02227-y · Cited by 57 · see citing works
Regulation of BDNF transcription by Nrf2 and MeCP2 ameliorates MPTP-induced neurotoxicity
Cao, Q., Zou, Q., Zhao, X. Y., Zhang, Y., Qu, Y., Wang, N., Murayama, S., Qi, Q., Hashimoto, K., Lin, S., et al. (2022) · Cell Death Discovery · doi:10.1038/s41420-022-01063-9 · Cited by 47 · see citing works
Discovery of Eicosapentaenoic Acid Esters of Hydroxy Fatty Acids as Potent Nrf2 Activators
Gowda, S. G. B., Fuda, H., Tsukui, T., Chiba, H., & Hui, S. (2020) · Antioxidants · doi:10.3390/antiox9050397 · Cited by 45 · see citing works
Ascorbic Acid Regulates the Immunity, Anti-Oxidation and Apoptosis in Abalone Haliotis discus hannai Ino
Luo, K., Li, X., Wang, L., Rao, W., Wu, Y., Liu, Y., Pan, M., Huang, D., Zhang, W., & Mai, K. (2021) · Antioxidants · doi:10.3390/antiox10091449 · Cited by 43 · see citing works
Social isolation after chronic unpredictable mild stress perpetuates depressive-like behaviors, memory deficits and social withdrawal via inhibiting ERK/KEAP1/NRF2 signaling
Si, L., Xiao, L., Xie, Y., Xu, H., Yuan, G., Xu, W., & Wang, G. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.12.092 · Cited by 44 · see citing works
Butyrate emerges as a crucial effector of Zhi-Zi-Chi decoctions to ameliorate depression via multiple pathways of brain-gut axis
Liu, J., Fang, Y., Cui, L.-X., Wang, Z., Luo, Y., Gao, C., Ge, W., Huang, T., Wen, J., & Zhou, T. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112861 · Cited by 46 · see citing works
Dietary Supplementation with Fish Oil or Conjugated Linoleic Acid Relieves Depression Markers in Mice by Modulation of the Nrf2 Pathway
Cigliano, L., Spagnuolo, M. S., Boscaino, F., Ferrandino, I., Monaco, A., Capriello, T., Cocca, E., Iannotta, L., Treppiccione, L., Luongo, D., et al. (2019) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201900243 · Cited by 42 · see citing works
Rapid-acting and long-lasting antidepressant-like action of (R)-ketamine in Nrf2 knock-out mice: a role of TrkB signaling
Qu, Y., Shan, J., Wang, S., Chang, L., Pu, Y., Wang, X., Tan, Y., Yamamoto, M. P., & Hashimoto, K. (2020) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-020-01208-w · Cited by 42 · see citing works
Molecular pathology associated with altered synaptic transcriptome in the dorsolateral prefrontal cortex of depressed subjects
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Sesamol ameliorates dextran sulfate sodium-induced depression-like and anxiety-like behaviors in colitis mice: the potential involvement of the gut–brain axis
Xia, B., Liu, X., Li, X., Wang, Y., Wang, D., Kou, R.-W., Zhang, L., Shi, R., Ye, J., Bo, X., et al. (2022) · Food & Function · doi:10.1039/d1fo03888e · Cited by 41 · see citing works
Recent Advances in the Early Intervention in Schizophrenia: Future Direction from Preclinical Findings
Hashimoto, K. (2019) · Current Psychiatry Reports · doi:10.1007/s11920-019-1063-7 · Cited by 40 · see citing works
The Nrf2 Pathway in Depressive Disorders: A Systematic Review of Animal and Human Studies
Sani, G., Margoni, S., Brugnami, A., Ferrara, O. M., Bernardi, E., Simonetti, A., Monti, L., Mazza, M., Janiri, D., Moccia, L., et al. (2023) · Antioxidants · doi:10.3390/antiox12040817 · Cited by 41 · see citing works
Xiaoyao Pills Ameliorate Depression-like Behaviors and Oxidative Stress Induced by Olfactory Bulbectomy in Rats via the Activation of the PIK3CA-AKT1-NFE2L2/BDNF Signaling Pathway
Ji, Y., Luo, J., Zeng, J., Fang, Y., Liu, R., Luan, F., & Zeng, N. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.643456 · Cited by 38 · see citing works
Beneficial effects of QTC-4-MeOBnE in an LPS-induced mouse model of depression and cognitive impairments: The role of blood-brain barrier permeability, NF-κB signaling, and microglial activation
Fronza, M. G., Baldinotti, R., Fetter, J., Rosa, S. G., Sacramento, M., Nogueira, C. W., Alves, D. A. C., Praticò, D., & Savegnago, L. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.10.002 · Cited by 37 · see citing works
Statins: Neurobiological underpinnings and mechanisms in mood disorders
Walker, A. J., Kim, Y., Borissiouk, I., Rehder, R., Dodd, S., Morris, G., Nierenberg, A. A., Maes, M., Fernandes, B. S., Dean, O. M., et al. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.07.012 · Cited by 33 · see citing works
Sulforaphane protects against skeletal muscle dysfunction in spontaneous type 2 diabetic db/db mice
Wang, M., Pu, D., Zhao, Y., Chen, J., Zhu, S., Lü, A., Liao, Z., Sun, Y., & Xiao, Q. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117823 · Cited by 35 · see citing works
Dietary intake of glucoraphanin during pregnancy and lactation prevents the behavioral abnormalities in the offspring after maternal immune activation
Fujita, Y., Fujita, A., Ishima, T., Hirai, A., Suzuki, S., Suganuma, H., & Hashimoto, K. (2020) · Neuropsychopharmacology Reports · doi:10.1002/npr2.12112 · Cited by 33 · see citing works
The Nrf2 pathway in psychiatric disorders: pathophysiological role and potential targeting
Bhandari, R., Kaur, J., Kaur, S., & Kuhad, A. (2021) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2021.1887141 · Cited by 32 · see citing works
Protective effects of sulforaphane against toxic substances and contaminants: A systematic review
Cascajosa-Lira, A., Prieto, A. I., Pichardo, S., Jos, A. M., & Cameán, A. M. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155731 · Cited by 31 · see citing works
Minocycline inhibits sleep deprivation-induced aberrant microglial activation and Keap1-Nrf2 expression in mouse hippocampus
Ahmed, A., Misrani, A. A., Tabassum, S., Yang, L., & Long, C. (2021) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2021.05.028 · Cited by 31 · see citing works
The compensatory antioxidant response system with a focus on neuroprogressive disorders
Morris, G., Puri, B. K., Walker, A. J., Berk, M., Walder, K. R., Bortolasci, C. C., Marx, W., Carvalho, A. F., & Maes, M. H. J. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2019.109708 · Cited by 31 · see citing works
Astaxanthin and Nrf2 Signaling Pathway: A Novel Target for New Therapeutic Approaches
Ashrafizadeh, M., Ahmadi, Z., Yaribeygi, H., Sathyapalan, T., & Sahebkar, A. (2021) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557521666210505112834 · Cited by 30 · see citing works
The Gut–Brain Axis as a Therapeutic Target in Multiple Sclerosis
Bugă, A. M., Pădureanu, V., Riza, A., Oancea, C. N., Albu, C. V., & Nica, A. D. (2023) · Cells · doi:10.3390/cells12141872 · Cited by 32 · see citing works
Mechanisms of repetitive transcranial magnetic stimulation for anti-depression: Evidence from preclinical studies
Luan, D., Zhao, M., Shi, Y., Li, L., Cao, Y.-J., Feng, H., & Zhang, Z. (2020) · World Journal of Psychiatry · doi:10.5498/wjp.v10.i10.223 · Cited by 29 · see citing works
Anti-Inflammatory and Neuroprotective Mechanisms of GTS-21, an α7 Nicotinic Acetylcholine Receptor Agonist, in Neuroinflammation and Parkinson’s Disease Mouse Models
Park, J., Leem, Y., Park, J., Kim, D., Kang, J. L., & Kim, H.-S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084420 · Cited by 29 · see citing works
Long-lasting beneficial effects of maternal intake of sulforaphane glucosinolate on gut microbiota in adult offspring
Wei, Y., Chang, L., Liu, G., Wang, X., Yang, Y. H., & Hashimoto, K. (2022) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2022.109098 · Cited by 27 · see citing works
Bdnf-Nrf-2 crosstalk and emotional behavior are disrupted in a sex-dependent fashion in adolescent mice exposed to maternal stress or maternal obesity
Musillo, C., Creutzberg, K. C., Collacchi, B., Ajmone‐Cat, M. A., Simone, R. D., Lepre, M., Amrein, I., Riva, M. A., Berry, A., & Cirulli, F. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02701-1 · Cited by 27 · see citing works
Bee Venom Activates the Nrf2/HO-1 and TrkB/CREB/BDNF Pathways in Neuronal Cell Responses against Oxidative Stress Induced by Aβ1–42
Nguyen, C. D., Yoo, J., Hwang, S., Cho, S.-Y., Kim, M., Jang, H., No, K. O., Shin, J. C., Kim, J., & Lee, G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031193 · Cited by 27 · see citing works
A role of splenic heme biosynthesis pathway in the persistent prophylactic actions of arketamine in lipopolysaccharide-treated mice
Ma, L., Wang, L., Qu, Y., Wan, X., & Hashimoto, K. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02564-6 · Cited by 26 · see citing works
Targeting NRF2 in Type 2 diabetes mellitus and depression: Efficacy of natural and synthetic compounds
Subba, R., Ahmad, M. H., Ghosh, B., & Mondal, A. C. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.174993 · Cited by 25 · see citing works
Flazin as a Promising Nrf2 Pathway Activator
Fuda, H., Miyanaga, S., Furukawa, T., Umetsu, S., Joko, S., Roan, Y., Hirotaka, S., Hui, S., Watanabe, M., & Chiba, H. (2019) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.9b04600 · Cited by 24 · see citing works
Treatment with Hydrogen-Rich Water Improves the Nociceptive and Anxio-Depressive-like Behaviors Associated with Chronic Inflammatory Pain in Mice
Coral-Pérez, S., Martínez-Martel, I., Martinez-Serrat, M., Batallé, G., Bai, X., Leite‐Panissi, C. R. A., & Pol, O. (2022) · Antioxidants · doi:10.3390/antiox11112153 · Cited by 23 · see citing works
Exploiting conjugated linoleic acid for health: a recent update
Chen, Y., Xiao, J., Zhu, X., Fan, X., Peng, M., Yang, M., Wang, C., Xia, L., & Zhou, M. (2024) · Food & Function · doi:10.1039/d4fo04911j · Cited by 21 · see citing works
Glyphosate exposure exacerbates the dopaminergic neurotoxicity in the mouse brain after repeated administration of MPTP
Pu, Y., Chang, L., Qu, Y., Wang, S., Tan, Y., Wang, X., Zhang, J., & Hashimoto, K. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.135032 · Cited by 19 · see citing works
Significant reduction of long non-coding RNAs expression in bipolar disorder
Maloum, Z., Taheri, M. N., Ghafouri‐Fard, S., & Shirvani-Farsani, Z. (2022) · BMC Psychiatry · doi:10.1186/s12888-022-03899-y · Cited by 19 · see citing works
Dietary intake of glucoraphanin prevents the reduction of dopamine transporter in the mouse striatum after repeated administration of MPTP
Pu, Y., Qu, Y., Chang, L., Wang, S., Zhang, K., Ushida, Y., Suganuma, H., & Hashimoto, K. (2019) · Neuropsychopharmacology Reports · doi:10.1002/npr2.12060 · Cited by 19 · see citing works
Repurposing Zileuton as a Depression Drug Using an AI and In Vitro Approach
Kubick, N., Pajares, M., Enache, I., Manda, G., & Mickael, M. (2020) · Molecules · doi:10.3390/molecules25092155 · Cited by 18 · see citing works
Electroacupuncture improves repeated social defeat stress-elicited social avoidance and anxiety-like behaviors by reducing Lipocalin-2 in the hippocampus
Chen, Y., Xie, S.-Y., Chen, C., & Lu, D. (2021) · Molecular Brain · doi:10.1186/s13041-021-00860-0 · Cited by 19 · see citing works
Early Diagnosis of Bipolar Disorder Coming Soon: Application of an Oxidative Stress Injury Biomarker (BIOS) Model
Niu, Z., Wu, X., Zhu, Y., Yang, L., Shi, Y., Wang, Y., Qiu, H. X., Gu, W., Wu, Y., Long, X., et al. (2022) · Neuroscience Bulletin · doi:10.1007/s12264-022-00871-4 · Cited by 19 · see citing works
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Authors: Hashimoto, K.
Affiliations: Chiba University (JP)
Corresponding author: Hashimoto, Kenji
ORCID: Hashimoto, Kenji
Venue: Frontiers in Pharmacology
Publisher: Frontiers Media SA
Published: 2018-10-16
Volume: 9
Pages: 1182-1182
ISSN: 1663-9812 (ISSN-L)
DOI: 10.3389/fphar.2018.01182
PMC: PMC6198170
OpenAlex: W2892958757
Cited by: 98
References: 106
Citations by year: 2026: 2 · 2025: 7 · 2024: 14 · 2023: 14 · 2022: 19 · 2021: 24 · 2020: 10 · 2019: 8
FWCI: 0.92
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: Frontiers in Pharmacology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Japan Society for the Promotion of Science London (17H04243)
Japan Agency for Medical Research and Development (JP18dm0107119)
Topics: Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Keywords: Nrf2/Keap1 pathway, depression, mood disorders, neuroinflammation, inflammatory cytokines, BDNF/TrkB signaling, sulforaphane, glucoraphanin, cruciferous vegetables, chronic social defeat stress, learned helplessness, stress resilience, hippocampus, prefrontal cortex, major depressive disorder, bipolar disorder, antidepressant effects

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Essential Role of Keap1-Nrf2 Signaling in Mood Disorders: Overview and Future Perspective

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