How Oxidative Stress Induces Depression?

Figures & data

Table 1 The Underlying Mechanisms of OS Induced Depression, as Revealed by Clinical Studies.

Table 2 The Underlying Mechanisms of OS Induced Depression, as Revealed by Rodent Studies.

Figure 1 Os causes depression through inducing mitochondrial impairment (A), neuroinflammation (B), glutamate excitotoxicity (C), BDNF/TrkB dysfunction (D) and 5-HT deficiency (E) in the brain, and the MGB disturbance (F) and the HPA axis dysregulation (G). A. Mitochondrial impairment induces central ATP deficiency, through elevating mtROS and reducing cardiolipin and ATP synthase, with astrocytes derived and mPFC localized ATP deficiency closely associated with depression. OS and mitochondria have mutual influence through mtROS, neuroinflammation and excess glutamate induced Ca²⁺ influx (A-OS). B. Neuroinflammation is characterized by microglia activation, pro-inflammatory cytokine expressions, etc. OS/Mitochondria-neuroinflammation interaction (AB, B-OS): Excess ROS increases pro-inflammatory cytokines, through elevating histone acetylation and activating NLRP3/caspase-1, AP-1 and NF-κB, and aberrant astrocytic OXPHOS activity; neuroinflammation promotes IDO/TDO/KMO to generate QUIN that activates NMDA, increases glutamate, triggers Ca²⁺ influx, which causes cytochrome C release and reduces SIRT3 activity and ATP generation, or depolarizes mitochondria membrane and generates excess ROS. C. Glutamate excitotoxicity is characterized by central synaptic accumulation. Glutamate-OS interaction (C-OS): Excess ROS results in excitotoxicity through affecting Ca²⁺, GS and GLT-1 expression; excess glutamate impairs mitochondria through NMDA activation and Ca²⁺ influx. Neuroinflammation-glutamate interaction (BC): Neuroinflammation promotes excitotoxicity through increasing microglial release or blocking astrocytic reuptake, by downregulating GLT-1 or elevating GLS and QUIN; excess glutamate might increase pro-inflammatory cytokines through NMDA/AMPA receptors, but reduce the cytokines through mGluRs. D. BDNF/TrkB dysfunction is characterized by inhibited BDNF expression and TrkB activation (PFC/hippocampus). BDNF-OS interaction (D-OS): Excess ROS inhibits BDNF expression, through reducing CREB and elevating NF-κB activity; BDNF owns antioxidant property through TrkB, ERK1/2 and NF-κB/sestrin2, thus, the dysfunction promotes OS. Neuroinflammation-BDNF/TrkB interaction (BD): NF-κB mediates LPS-reduced BDNF expression through interacting with BDNF/TrkB; BDNF promotes TNF-α and IL-1β release by activating astrocytes and microglia. Glutamate-BDNF/TrkB interaction (CD): Excess glutamate might inhibit BDNF expression by activating extra-synaptic NMDA and eEF2; BDNF promotes the release or protects neurons against the excitotoxicity of glutamate, through PI3K, PLC-γ, ERK, etc., whose dysfunction weakens the influence correspondingly. E. Central 5-HT interacts with multiple aspects, whose deficiency attenuates the influence correspondingly: 5-HT presents antioxidant properties, while OS inhibits 5-HT through neuroinflammation and MGB disturbance (E-OS); Neuroinflammation inhibits 5-HT by promoting KP and modulating 5-HTT (BE); 5-HT inhibits glutamate transmission through 5-HT 1A/B receptor, which in turn regulates 5-HT function through VGLUT1 (CE); 5-HT promotes BDNF expression and TrkB activation, while BDNF affects 5-HTT function (DE). F. MGB disturbance is characterized by disturbed microbiota composition/metabolism. MGB-OS/mitochondria interaction (AF, F-OS): Microbiota affects ROS generation by modulating activities of NOX, SCFAs and antioxidants, and mitochondria metabolism; Mitochondrial genotype/mutation affects microbiota through mtROS. Neuroinflammation-MGB interaction (BF): MGB disturbance leads to gut inflammation, increases QUIN that damages BBB and results in neuroinflammation; Neuroinflammation disturbs microbiota homeostasis, through pro-inflammatory cytokines and NLRP3. BDNF-MGB interaction (DF): BDNF modulates intestinal barrier integrity; MGB disturbance reduces hippocampal BDNF expression. 5-HT-MGB interaction (EF): Microbiota disturbance inhibits 5-HT generation, by promoting intestinal/central KP, affecting 5-HT and TPH 1 gene expressions; 5-HTT genotype modulates microbiota composition. G. HPA axis interacts with multiple aspects, whose dysregulation attenuates the influence correspondingly: HPA affects ROS generation, mitochondria gene expression and metabolism through GRs, while NO mediates IL-1β and cholinergic stimulation of HPA (G-OS); HPA interacts with neuroinflammation through cytokines and GR/NF-κB signaling (BG); HPA affects glutamate release (through GR-TrkB interaction) and related gene expression (CG); GR activation reduces BDNF expression, while BDNF affects GR phosphorylation and rewrote glucocorticoid transcriptome (DG); HPA hormones increase intestinal barrier permeability and disturb microbiota composition, while MGB affects HPA through GABAergic activity (FG). AB, BC, CD, DE, EF and AF have indirect interaction through OS. AP-1 = activating protein-1; AMPA = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic; ATP = adenosine triphosphate; BDNF = brain-derived neurotrophic factor; CREB = cAMP responsive element binding protein; EAATs = excitatory amino acid transporters; eEF2 = eukaryotic elongation factor 2; ERK = extracellular signal-related kinases; GS = glutamine synthetase; GLS = glutaminase; Glu = glutamate; GLT-1 = glutamate transporter 1; IDO = indoleamine 2,3-dioxygenase; IL-1β = interleukin-1β; IL-6 = interleukin-6; KMO = kynurenine 3-monooxygenase; KP = kynurenine pathway; MGB = microbial-gut-brain; mPFC = medial prefrontal cortex; mtROS = mitochondrial ROS; NF-κB = nuclear factor kappa-B; NLRP3 = NOD-like receptor thermal protein domain associated protein 3; NMDA = N-methyl-D-aspartic acid; NOX = NADPH oxidase; OS = oxidative stress; OXPHOS = oxidative phosphorylation; PLC-γ = phospholipase C-γ; PKC = protein kinase C; PI3K = phosphatidylinositide 3-kinase; PVN = paraventricular nucleus; QUIN = quinolinic acid; RNS = reactive nitrogen species; ROS = reactive oxygen species; SCFAs = short-chain fatty acids; SIRT3 = sirtuin 3; SRC =sparse representation-based classification; TDO =tryptophan-2,3-dioxygenase; TPH = tryptophan hydroxylase; TNF-α = tumor necrosis factor-α; TrkB = tyrosine kinase B; TRYCATs = tryptophan catabolites; VGLUT1 = vesicular glutamate transporter 1; 5-HTT = serotonin transporter.

Nayernia Z., Jaquet V., Krause K. H. (2014). New insights on NOX enzymes in the central nervous system. Antioxidants & Redox Signaling, 20(17), 2815–2837. https://doi.org/10.1089/ars.2013.5703

 PubMed Web of Science ®Google Scholar

Lindqvist D., Dhabhar F. S., James S. J., Hough C. M., Jain F. A., Bersani F. S., Reus V. I., Verhoeven J. E., Epel E. S., Mahan L., Rosser R., Wolkowitz O. M., Mellon S. H. (2017). Oxidative stress, inflammation and treatment response in major depression. Psychoneuroendocrinology, 76, 197–205. https://doi.org/10.1016/j.psyneuen.2016.11.031

 PubMed Web of Science ®Google Scholar

Du J., McEwen B., Manji H. K. (2009). Glucocorticoid receptors modulate mitochondrial function: A novel mechanism for neuroprotection. Communicative & Integrative Biology, 2(4), 350–352. https://doi.org/10.4161/cib.2.4.8554

 PubMedGoogle Scholar

Camkurt M. A., Fındıklı E., İzci F., Kurutaş E. B., Tuman T. C. (2016). Evaluation of malondialdehyde, superoxide dismutase and catalase activity and their diagnostic value in drug naïve, first episode, non-smoker major depression patients and healthy controls. Psychiatry Research, 238, 81–85. https://doi.org/10.1016/j.psychres.2016.01.075

 PubMed Web of Science ®Google Scholar

Gao K., Farzi A., Ke X., Yu Y., Chen C., Chen S., Yu T., Wang H., Li Y. (2022). Oral administration of Lactococcus lactis WHH2078 alleviates depressive and anxiety symptoms in mice with induced chronic stress. Food & Function, 13(2), 957–969. https://doi.org/10.1039/d1fo03723d

 PubMed Web of Science ®Google Scholar

Bailey M. T., Dowd S. E., Galley J. D., Hufnagle A. R., Allen R. G., Lyte M. (2011). Exposure to a social stressor alters the structure of the intestinal microbiota: Implications for stressor-induced immunomodulation. Brain, Behavior, and Immunity, 25(3), 397–407. https://doi.org/10.1016/j.bbi.2010.10.023

 PubMed Web of Science ®Google Scholar

Allen J., Romay-Tallon R., Brymer K. J., Caruncho H. J., Kalynchuk L. E. (2018). Mitochondria and mood: Mitochondrial dysfunction as a key player in the manifestation of depression. Frontiers in Neuroscience, 12, 386. https://doi.org/10.3389/fnins.2018.00386

 PubMed Web of Science ®Google Scholar

Berton O., Nestler E. J. (2006). New approaches to antidepressant drug discovery: Beyond monoamines. Nature Reviews Neuroscience, 7(2), 137–151. https://doi.org/10.1038/nrn1846

 PubMed Web of Science ®Google Scholar

Gaidin S. G., Turovskaya M. V., Gavrish M. S., Babaev A. A., Mal’tseva V. N., Blinova E. V., Turovsky E. A. (2020). The selective BDNF overexpression in neurons protects neuroglial networks against OGD and glutamate-induced excitotoxicity. International Journal of Neuroscience, 130(4), 363–383. https://doi.org/10.1080/00207454.2019.1691205

 PubMed Web of Science ®Google Scholar

Popova N. K., Naumenko V. S. (2019). Neuronal and behavioral plasticity: The role of serotonin and BDNF systems tandem. Expert Opinion on Therapeutic Targets, 23(3), 227–239. https://doi.org/10.1080/14728222.2019.1572747

 PubMed Web of Science ®Google Scholar

Enache D., Pariante C. M., Mondelli V. (2019). Markers of central inflammation in major depressive disorder: A systematic review and meta-analysis of studies examining cerebrospinal fluid, positron emission tomography and post-mortem brain tissue. Brain, Behavior, and Immunity, 81, 24–40. https://doi.org/10.1016/j.bbi.2019.06.015

 PubMed Web of Science ®Google Scholar

Gritti D., Delvecchio G., Ferro A., Bressi C., Brambilla P. (2021). Neuroinflammation in major depressive disorder: A review of PET imaging studies examining the 18-kDa translocator protein. Journal of Affective Disorders, 292, 642–651. https://doi.org/10.1016/j.jad.2021.06.001

 PubMed Web of Science ®Google Scholar

Ma H., Xu J., Li R., McIntyre R. S., Teopiz K. M., Cao B., Yang F. (2022). The impact of cognitive behavioral therapy on peripheral interleukin-6 levels in depression: A systematic review and meta-analysis. Frontiers in Psychiatry, 13, 844176. https://doi.org/10.3389/fpsyt.2022.844176

 PubMed Web of Science ®Google Scholar

Garcia-Garcia M. L., Tovilla-Zarate C. A., Villar-Soto M., Juarez-Rojop I. E., Gonzalez-Castro T. B., Genis-Mendoza A. D., Ramos-Mendez M. A., Lopez-Narvaez M. L., Saucedo-Osti A. S., Ruiz-Quinones J. A., Martinez-Magana J. J. (2022). Fluoxetine modulates the pro-inflammatory process of IL-6, IL-1beta and TNF-alpha levels in individuals with depression: A systematic review and meta-analysis. Psychiatry Research, 307, 114317. https://doi.org/10.1016/j.psychres.2021.114317

 PubMed Web of Science ®Google Scholar

Dionisie V., Filip G. A., Manea M. C., Manea M., Riga S. (2021). The anti-inflammatory role of SSRI and SNRI in the treatment of depression: A review of human and rodent research studies. Inflammopharmacology, 29(1), 75–90. https://doi.org/10.1007/s10787-020-00777-5

 PubMed Web of Science ®Google Scholar

Madeira C., Vargas-Lopes C., Brandao C. O., Reis T., Laks J., Panizzutti R., Ferreira S. T. (2018). Elevated glutamate and glutamine levels in the cerebrospinal fluid of patients with probable Alzheimer’s disease and depression. Frontiers in Psychiatry, 9, 561. https://doi.org/10.3389/fpsyt.2018.00561

 PubMed Web of Science ®Google Scholar

Fukumoto K., Fogaça M. V., Liu R. J., Duman C., Kato T., Li X. Y., Duman R. S. (2019). Activity-dependent brain-derived neurotrophic factor signaling is required for the antidepressant actions of (2R,6R)-hydroxynorketamine. Proceedings of the National Academy of Sciences, 116(1), 297–302. https://doi.org/10.1073/pnas.1814709116

 PubMed Web of Science ®Google Scholar

Guo L. T., Wang S. Q., Su J., Xu L. X., Ji Z. Y., Zhang R. Y., Zhao Q. W., Ma Z. Q., Deng X. Y., Ma S. P. (2019). Baicalin ameliorates neuroinflammation-induced depressive-like behavior through inhibition of toll-like receptor 4 expression via the PI3K/AKT/FoxO1 pathway. Journal of Neuroinflammation, 16(1), 95. https://doi.org/10.1186/s12974-019-1474-8

 PubMed Web of Science ®Google Scholar

Sanada K., Nakajima S., Kurokawa S., Barceló-Soler A., Ikuse D., Hirata A., Yoshizawa A., Tomizawa Y., Salas-Valero M., Noda Y., Mimura M., Iwanami A., Kishimoto T. (2020). Gut microbiota and major depressive disorder: A systematic review and meta-analysis. Journal of Affective Disorders, 266, 1–13. https://doi.org/10.1016/j.jad.2020.01.102

 PubMed Web of Science ®Google Scholar

Barandouzi Z. A., Starkweather A. R., Henderson W. A., Gyamfi A., Cong X. S. (2020). Altered composition of gut microbiota in depression: A systematic review. Frontiers in Psychiatry, 11, 541. https://doi.org/10.3389/fpsyt.2020.00541

 PubMed Web of Science ®Google Scholar

Otte C., Gold S. M., Penninx B. W., Pariante C. M., Etkin A., Fava M., Mohr D. C., Schatzberg A. F. (2016). Major depressive disorder. Nature Reviews Disease Primers, 2(1), 16065. https://doi.org/10.1038/nrdp.2016.65

 PubMed Web of Science ®Google Scholar

Parul M. A., Singh S., Singh S., Tiwari V., Chaturvedi S., Wahajuddin M., Palit G., Shukla S. (2021). Chronic unpredictable stress negatively regulates hippocampal neurogenesis and promote anxious depression-like behavior via upregulating apoptosis and inflammatory signals in adult rats. Brain Research Bulletin, 172, 164–179. https://doi.org/10.1016/j.brainresbull.2021.04.017

 PubMed Web of Science ®Google Scholar

Montanari M., Martella G., Bonsi P., Meringolo M. (2022). Autism spectrum disorder: focus on glutamatergic neurotransmission. International Journal of Molecular Sciences, 23(7), 3861. https://doi.org/10.3390/ijms23073861

 PubMed Web of Science ®Google Scholar

Park S. S., Park H. S., Kim C. J., Baek S. S., Kim T. W. (2019). Exercise attenuates maternal separation-induced mood disorder-like behaviors by enhancing mitochondrial functions and neuroplasticity in the dorsal raphe. Behavioural Brain Research, 372, 112049. https://doi.org/10.1016/j.bbr.2019.112049

 PubMed Web of Science ®Google Scholar

Xie X., Shen Q., Yu C., Xiao Q., Zhou J., Xiong Z., Li Z., Fu Z. (2020). Depression-like behaviors are accompanied by disrupted mitochondrial energy metabolism in chronic corticosterone-induced mice. The Journal of Steroid Biochemistry and Molecular Biology, 200, 105607. https://doi.org/10.1016/j.jsbmb.2020.105607

 PubMed Web of Science ®Google Scholar

Bravo J. A., Forsythe P., Chew M. V., Escaravage E., Savignac H. M., Dinan T. G., Bienenstock J., Cryan J. F. (2011). Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences, 108(38), 16050–16055. https://doi.org/10.1073/pnas.1102999108

 PubMed Web of Science ®Google Scholar

Herken H., Gurel A., Selek S., Armutcu F., Ozen M. E., Bulut M., Kap O., Yumru M., Savas H. A., Akyol O. (2007). Adenosine deaminase, nitric oxide, superoxide dismutase, and xanthine oxidase in patients with major depression: Impact of antidepressant treatment. Archives of Medical Research, 38(2), 247–252. https://doi.org/10.1016/j.arcmed.2006.10.005

 PubMed Web of Science ®Google Scholar

Xie X., Yu C., Zhou J., Xiao Q., Shen Q., Xiong Z., Li Z., Fu Z. (2020). Nicotinamide mononucleotide ameliorates the depression-like behaviors and is associated with attenuating the disruption of mitochondrial bioenergetics in depressed mice. Journal of Affective Disorders, 263, 166–174. https://doi.org/10.1016/j.jad.2019.11.147

 PubMed Web of Science ®Google Scholar

Giridharan V. V., Reus G. Z., Selvaraj S., Scaini G., Barichello T., Quevedo J. (2019). Maternal deprivation increases microglial activation and neuroinflammatory markers in the prefrontal cortex and hippocampus of infant rats. Journal of Psychiatric Research, 115, 13–20. https://doi.org/10.1016/j.jpsychires.2019.05.001

 PubMed Web of Science ®Google Scholar

Pan Y., Chen X. Y., Zhang Q. Y., Kong L. D. (2014). Microglial NLRP3 inflammasome activation mediates IL-1β-related inflammation in prefrontal cortex of depressive rats. Brain, Behavior, and Immunity, 41, 90–100. https://doi.org/10.1016/j.bbi.2014.04.007

 PubMed Web of Science ®Google Scholar

Duda W., Kubera M., Kreiner G., Curzytek K., Detka J., Glombik K., Slusarczyk J., Basta-Kaim A., Budziszewska B., Lason W., Regulska M., Leskiewicz M., Roman A., Zelek-Molik A., Nalepa I. (2017). Suppression of pro-inflammatory cytokine expression and lack of anti-depressant-like effect of fluoxetine in lipopolysaccharide-treated old female mice. International Immunopharmacology, 48, 35–42. https://doi.org/10.1016/j.intimp.2017.04.021

 PubMed Web of Science ®Google Scholar

Liu S., Xu S., Wang Z., Guo Y., Pan W., Shen Z. (2018). Anti-depressant-like effect of sinomenine on chronic unpredictable mild stress-induced depression in a mouse model. Medical Science Monitor, 24, 7646–7653. https://doi.org/10.12659/MSM.908422

 PubMed Web of Science ®Google Scholar

Kundu P., Blacher E., Elinav E., Pettersson S. (2017). Our gut microbiome: The evolving inner self. Cell, 171(7), 1481–1493. https://doi.org/10.1016/j.cell.2017.11.024

 PubMed Web of Science ®Google Scholar

Chen H., Amazit L., Lombès M., Le Menuet D. (2019). Crosstalk between glucocorticoid receptor and early-growth response protein 1 accounts for repression of brain-derived neurotrophic factor transcript 4 expression. Neuroscience, 399, 12–27. https://doi.org/10.1016/j.neuroscience.2018.12.012

 PubMed Web of Science ®Google Scholar

Fan J., Guo F., Mo R., Chen L. Y., Mo J., Lu C. L., Ren J., Zhong Q., Kuang X., Wen Y., Gu T. T., Liu J., Li S., Fang Y., Zhao C., Gao T. M., Cao X. (2023). O-GlcNAc transferase in astrocytes modulates depression-related stress susceptibility through glutamatergic synaptic transmission. Journal of Clinical Investigation, 133(7). https://doi.org/10.1172/jci160016

 Web of Science ®Google Scholar

Freimer D., Yang T. T., Ho T. C., Tymofiyeva O., Leung C. (2022). The gut microbiota, HPA axis, and brain in adolescent-onset depression: Probiotics as a novel treatment. Brain, Behavior, & Immunity - Health, 26, 100541. https://doi.org/10.1016/j.bbih.2022.100541

 PubMedGoogle Scholar

Hollis F., Pope B. S., Gorman-Sandler E., Wood S. K. (2022). Neuroinflammation and mitochondrial dysfunction link social stress to depression. Curr Top Behav Neurosci, 54, 59–93. https://doi.org/10.1007/7854_2021_300

 PubMedGoogle Scholar

Yang F., Wang H., Chen H., Ran D., Tang Q., Weng P., Sun Y., Jiang W. (2020). RAGE Signaling pathway in hippocampus dentate gyrus involved in GLT-1 decrease induced by chronic unpredictable stress in rats. Brain Research Bulletin, 163, 49–56. https://doi.org/10.1016/j.brainresbull.2020.06.020

 PubMed Web of Science ®Google Scholar

Bai Z., Gao T., Zhang R., Lu Y., Tian J., Wang T., Zhao K., Wang H. (2023). Inhibition of IL-6 methylation by Saikosaponin C regulates neuroinflammation to alleviate depression. International Immunopharmacology, 118, 110043. https://doi.org/10.1016/j.intimp.2023.110043

 PubMed Web of Science ®Google Scholar

Correia A. S., Vale N. (2022). Tryptophan metabolism in depression: A narrative review with a focus on serotonin and kynurenine pathways. International Journal of Molecular Sciences, 23(15), 8493. https://doi.org/10.3390/ijms23158493

 PubMed Web of Science ®Google Scholar

Atlante A., Calissano P., Bobba A., Giannattasio S., Marra E., Passarella S. (2001). Glutamate neurotoxicity, oxidative stress and mitochondria. FEBS Letters, 497(1), 1–5. https://doi.org/10.1016/s0014-5793(01)02437-1

 PubMed Web of Science ®Google Scholar

Huang Y., Wang Y., Wang H., Liu Z., Yu X., Yan J., Yu Y., Kou C., Xu X., Lu J., Wang Z., He S., Xu Y., He Y., Li T., Guo W., Tian H., Xu G., Xu X., Ma Y., Wang L., Wang L., Yan Y., Wang B., Xiao S., Zhou L., Li L., Tan L., Zhang T., Ma C., Li Q., Ding H., Geng H., Jia F., Shi J., Wang S., Zhang N., Du X., Du X., Wu Y. (2019). Prevalence of mental disorders in China: A cross-sectional epidemiological study. The Lancet Psychiatry, 6(3), 211–224. https://doi.org/10.1016/S2215-0366(18)30511-X

 PubMed Web of Science ®Google Scholar

de Foubert G., O’Neill M. J., Zetterström T. S. (2007). Acute onset by 5-HT(6)-receptor activation on rat brain brain-derived neurotrophic factor and activity-regulated cytoskeletal-associated protein mRNA expression. Neuroscience, 147(3), 778–785. https://doi.org/10.1016/j.neuroscience.2007.04.045

 PubMed Web of Science ®Google Scholar

Lepack A. E., Fuchikami M., Dwyer J. M., Banasr M., Duman R. S. (2014). BDNF release is required for the behavioral actions of ketamine. International Journal of Neuropsychopharmacology, 18(1), pyu033–pyu033. https://doi.org/10.1093/ijnp/pyu033.

 PubMed Web of Science ®Google Scholar

Brunt V. E., Gioscia-Ryan R. A., Richey J. J., Zigler M. C., Cuevas L. M., Gonzalez A., Vázquez-Baeza Y., Battson M. L., Smithson A. T., Gilley A. D., Ackermann G., Neilson A. P., Weir T., Davy K. P., Knight R., Seals D. R. (2019). Suppression of the gut microbiome ameliorates age-related arterial dysfunction and oxidative stress in mice. The Journal of Physiology, 597(9), 2361–2378. https://doi.org/10.1113/jp277336

 PubMed Web of Science ®Google Scholar

Hoban A. E., Moloney R. D., Golubeva A. V., McVey Neufeld K. A., O’Sullivan O., Patterson E., Stanton C., Dinan T. G., Clarke G., Cryan J. F. (2016). Behavioural and neurochemical consequences of chronic gut microbiota depletion during adulthood in the rat. Neuroscience, 339, 463–477. https://doi.org/10.1016/j.neuroscience.2016.10.003

 PubMed Web of Science ®Google Scholar

Kelly J. R., Borre Y., O’Brien C., Patterson E., El Aidy S., Deane J., Kennedy P. J., Beers S., Scott K., Moloney G., Hoban A. E., Scott L., Fitzgerald P., Ross P., Stanton C., Clarke G., Cryan J. F., Dinan T. G. (2016). Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. Journal of Psychiatric Research, 82, 109–118. https://doi.org/10.1016/j.jpsychires.2016.07.019

 PubMed Web of Science ®Google Scholar

Lafon-Cazal M., Pietri S., Culcasi M., Bockaert J. (1993). NMDA-dependent superoxide production and neurotoxicity. Nature, 364(6437), 535–537. https://doi.org/10.1038/364535a0

 PubMed Web of Science ®Google Scholar

Zhu X., Sakamoto S., Ishii C., Smith M. D., Ito K., Obayashi M., Unger L., Hasegawa Y., Kurokawa S., Kishimoto T., Li H., Hatano S., Wang T. H., Yoshikai Y., Kano S. I., Fukuda S., Sanada K., Calabresi P. A., Kamiya A. (2023). Dectin-1 signaling on colonic γδ T cells promotes psychosocial stress responses. Nature Immunology, 24(4), 625–636. https://doi.org/10.1038/s41590-023-01447-8

 PubMed Web of Science ®Google Scholar

Hooper L. V., Littman D. R., Macpherson A. J. (2012). Interactions between the microbiota and the immune system. Science, 336(6086), 1268–1273. https://doi.org/10.1126/science.1223490

 PubMed Web of Science ®Google Scholar

Yang C., Fujita Y., Ren Q., Ma M., Dong C., Hashimoto K. (2017). Bifidobacterium in the gut microbiota confer resilience to chronic social defeat stress in mice. Scientific Reports, 7, 45942. https://doi.org/10.1038/srep45942

 PubMed Web of Science ®Google Scholar

Deltheil T., Guiard B. P., Cerdan J., David D. J., Tanaka K. F., Repérant C., Guilloux J. P., Coudoré F., Hen R., Gardier A. M. (2008). Behavioral and serotonergic consequences of decreasing or increasing hippocampus brain-derived neurotrophic factor protein levels in mice. Neuropharmacology, 55(6), 1006–1014. https://doi.org/10.1016/j.neuropharm.2008.08.001

 PubMed Web of Science ®Google Scholar