The Bioactive Dietary Polyphenol Preparation Alleviates Depression and Anxiety-Like Behaviors by Modulating the Regional Heterogeneity of Microglia Morphology

Overview

Journal Mol Nutr Food Res

Specialty Nutritional Sciences

Date 2023 Jul 13

PMID 37439457

Authors

Eun-Jeong Yang

Tal Frolinger

Umar Haris Iqbal

James Murrough

Giulio M Pasinetti

Affiliations

Soon will be listed here.

Abstract

Scope: The goal of this study is to investigate the effects of a bioactive dietary polyphenol preparation (BDPP), which is made up of grape-derived polyphenols, on microglial responses, as well as the underlying molecular mechanisms in depression and anxiety-like behaviors.

Methods And Results: The study finds that treatment with BDPP significantly decreases depression-like and anxiety-like behaviors induced by chronic stress in mice, while leaving their locomotor activity unaffected. The study also finds that BDPP treatment reverses microglia activation in the amygdala and hippocampal formation, regions of the brain involved in emotional regulation, from an amoeboid shape to ramified shape. Additionally, BDPP treatment modulates the release of pro-inflammatory cytokines such as interleukin-6 via high mobility box 1 protein and the receptor for advanced glycation end products (HMGB1-RAGE) signaling pathway in activated microglia induced by chronic stress.

Conclusion: The findings suggest regional heterogeneity in microglial responses following chronic stress in subregions of the corticolimbic circuit. Specifically, activation of the immune-inflammatory HMGB1-RAGE pathway may provide a new avenue for preventing the manifestation of psychiatric impairments including stress-induced anxiety- and depression-like behavior, using bioactive and bioavailable polyphenols.

Citing Articles

The role of gut microbiota and metabolomic pathways in modulating the efficacy of SSRIs for major depressive disorder.

Jiang Y, Qu Y, Shi L, Ou M, Du Z, Zhou Z Transl Psychiatry. 2024; 14(1):493.

PMID: 39695082 PMC: 11655517. DOI: 10.1038/s41398-024-03208-z.

Microbiome and Metabolite Analysis Insight into the Potential of Shrimp Head Hydrolysate to Alleviate Depression-like Behaviour in Growth-Period Mice Exposed to Chronic Stress.

Hu L, Ye W, Deng Q, Wang C, Luo J, Huang L Nutrients. 2024; 16(12).

PMID: 38931307 PMC: 11206410. DOI: 10.3390/nu16121953.

Coffee polyphenols ameliorate early-life stress-induced cognitive deficits in male mice.

Geertsema J, Kratochvil M, Gonzalez-Dominguez R, Lefevre-Arbogast S, Low D, Du Preez A Neurobiol Stress. 2024; 31:100641.

PMID: 38827176 PMC: 11140806. DOI: 10.1016/j.ynstr.2024.100641.

The Phytoneuroendocrine System: Connecting Plants to Human Systems Biology.

Minich D Integr Med (Encinitas). 2024; 23(1):28-31.

PMID: 38618161 PMC: 11007616.

References

Pontifex M, Malik M, Connell E, Muller M, Vauzour D . Citrus Polyphenols in Brain Health and Disease: Current Perspectives. Front Neurosci. 2021; 15:640648. PMC: 7933480. DOI: 10.3389/fnins.2021.640648. View

Wang J, Hodes G, Zhang H, Zhang S, Zhao W, Golden S . Epigenetic modulation of inflammation and synaptic plasticity promotes resilience against stress in mice. Nat Commun. 2018; 9(1):477. PMC: 5797143. DOI: 10.1038/s41467-017-02794-5. View

Bordt E, Block C, Petrozziello T, Sadri-Vakili G, Smith C, Edlow A . Isolation of Microglia from Mouse or Human Tissue. STAR Protoc. 2020; 1(1). PMC: 7416840. DOI: 10.1016/j.xpro.2020.100035. View

Kaufmann F, Costa A, Ghisleni G, Diaz A, Rodrigues A, Peluffo H . NLRP3 inflammasome-driven pathways in depression: Clinical and preclinical findings. Brain Behav Immun. 2017; 64:367-383. DOI: 10.1016/j.bbi.2017.03.002. View

Jia C, Zhang J, Chen H, Zhuge Y, Chen H, Qian F . Endothelial cell pyroptosis plays an important role in Kawasaki disease via HMGB1/RAGE/cathespin B signaling pathway and NLRP3 inflammasome activation. Cell Death Dis. 2019; 10(10):778. PMC: 6791856. DOI: 10.1038/s41419-019-2021-3. View

Li S, Yin S, Ding H, Shao Y, Zhou S, Pu W . Polyphenols as potential metabolism mechanisms regulators in liver protection and liver cancer prevention. Cell Prolif. 2022; 56(1):e13346. DOI: 10.1111/cpr.13346. View

Lin K, Li Y, Du Toit E, Wendt L, Sun J . Effects of Polyphenol Supplementations on Improving Depression, Anxiety, and Quality of Life in Patients With Depression. Front Psychiatry. 2021; 12:765485. PMC: 8606635. DOI: 10.3389/fpsyt.2021.765485. View

Tian J, Avalos A, Mao S, Chen B, Senthil K, Wu H . Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol. 2007; 8(5):487-96. DOI: 10.1038/ni1457. View

Franklin T, Wohleb E, Zhang Y, Fogaca M, Hare B, Duman R . Persistent Increase in Microglial RAGE Contributes to Chronic Stress-Induced Priming of Depressive-like Behavior. Biol Psychiatry. 2017; 83(1):50-60. PMC: 6369917. DOI: 10.1016/j.biopsych.2017.06.034. View

10.

Vauzour D . Dietary polyphenols as modulators of brain functions: biological actions and molecular mechanisms underpinning their beneficial effects. Oxid Med Cell Longev. 2012; 2012:914273. PMC: 3372091. DOI: 10.1155/2012/914273. View

11.

Toenders Y, Laskaris L, Davey C, Berk M, Milaneschi Y, Lamers F . Inflammation and depression in young people: a systematic review and proposed inflammatory pathways. Mol Psychiatry. 2021; 27(1):315-327. DOI: 10.1038/s41380-021-01306-8. View

12.

Krikorian R, Nash T, Shidler M, Shukitt-Hale B, Joseph J . Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment. Br J Nutr. 2009; 103(5):730-4. DOI: 10.1017/S0007114509992364. View

13.

Niraula A, Sheridan J, Godbout J . Microglia Priming with Aging and Stress. Neuropsychopharmacology. 2016; 42(1):318-333. PMC: 5143497. DOI: 10.1038/npp.2016.185. View

14.

Agnello D, Wang H, Yang H, Tracey K, Ghezzi P . HMGB-1, a DNA-binding protein with cytokine activity, induces brain TNF and IL-6 production, and mediates anorexia and taste aversion. Cytokine. 2002; 18(4):231-6. DOI: 10.1006/cyto.2002.0890. View

15.

Westfall S, Caracci F, Estill M, Frolinger T, Shen L, Pasinetti G . Chronic Stress-Induced Depression and Anxiety Priming Modulated by Gut-Brain-Axis Immunity. Front Immunol. 2021; 12:670500. PMC: 8264434. DOI: 10.3389/fimmu.2021.670500. View

16.

Tan Y, Yuan Y, Tian L . Microglial regional heterogeneity and its role in the brain. Mol Psychiatry. 2019; 25(2):351-367. PMC: 6974435. DOI: 10.1038/s41380-019-0609-8. View

17.

Figueira I, Garcia G, Pimpao R, Terrasso A, Costa I, Almeida A . Correction to: Polyphenols journey through blood-brain barrier towards neuronal protection. Sci Rep. 2021; 11(1):17112. PMC: 8373959. DOI: 10.1038/s41598-021-96179-w. View

18.

Beurel E, Toups M, Nemeroff C . The Bidirectional Relationship of Depression and Inflammation: Double Trouble. Neuron. 2020; 107(2):234-256. PMC: 7381373. DOI: 10.1016/j.neuron.2020.06.002. View

19.

Ho L, Cheng H, Wang J, Simon J, Wu Q, Zhao D . A Comprehensive Database and Analysis Framework To Incorporate Multiscale Data Types and Enable Integrated Analysis of Bioactive Polyphenols. Mol Pharm. 2017; 15(3):840-850. PMC: 6016761. DOI: 10.1021/acs.molpharmaceut.7b00412. View

20.

Westfall S, Pasinetti G . The Gut Microbiota Links Dietary Polyphenols With Management of Psychiatric Mood Disorders. Front Neurosci. 2019; 13:1196. PMC: 6848798. DOI: 10.3389/fnins.2019.01196. View