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Quercetin Alleviates Demyelination Through Regulating Microglial Phenotype Transformation to Mitigate Neuropsychiatric Symptoms in Mice with Vascular Dementia

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Abstract

Cerebral hypoperfusion plays a pivotal role in the ictus and development of vascular dementia (VaD) with neuropsychiatric symptoms. To date, few pharmacological interventions for neuropsychiatric symptoms are available in the VaD patients with neuropsychiatric impairments. Here, our results demonstrated that the extent of demyelination was dramatically deteriorated and the thickness of myelin sheath was evidently decreased in the presence of cerebral hypoperfusion, whereas Quercetin possessed the potential of abrogating these effects at least in part, then relieving anxiety and depression-like behavior when mice exposed to bilateral carotid artery stenosis (BCAS)/chronic restraint stress (CRS). The underlying mechanism was that Quercetin facilitated secretion of anti-inflammatory cytokines (IL-4 and IL-10) and in turn decreased production of pro-inflammatory factors (TNF-α and IL-1β) due to regulating microglial phenotype transformation, thereafter enhancing the microglial engulfment ability of myelin fragments in vitro and in vivo. Collectively, the results demonstrated that that Quercetin mediated microglial transformation into anti-inflammatory phenotype to reduce demyelination in ventral hippocampus (vHIP), thereafter mitigating neuropsychiatric deficits (including anxiety and depression). The present research broadens the therapeutic scope of Quercetin in central nervous system (CNS) disorders with presence of white matter damage and/or the insufficient activation of anti-inflammatory microglia, particularly for vascular dementia with/without neuropsychiatric symptoms.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Abbreviations

VaD:

Vascular dementia

BCAS:

Bilateral caratid artery stenosis

CRS:

Chronic restraint stress

vHIP:

Ventral hippocampus

CNS:

Central nervous system

BCCAO:

Bilateral common carotid arteries occlusion

VCI:

Vascular cognitive impairment

MS:

Multiple sclerosis

AD:

Alzheimer’s disease

OPCs:

Oligodendrocyte precursor cells

OGD:

Oxygen/glucose deprivation

SCI:

Spinal cord injury

CA1:

Hippocampal cornu ammonis

DG:

Dentate gyrus

TEM:

Trasmission electron microscopy

LFB:

Klüver-Barrera Luxol Fast Blue

PFA:

Paraformaldehyde

BSA:

Bovine serum album

DAPI:

4’,6-Diamidino-2-phenylindole

ELISA:

Enzyme-linked immunorbent assay

TST:

Tail suspension test

FST:

Forced swimming test

SPT:

Sucrose preference test

EPM:

Elevated plus maze

OFT:

Open field test

References

  1. O’Brien JT, Thomas A (2015) Vascular dementia. Lancet (London, England) 386(10004):1698–1706. https://doi.org/10.1016/s0140-6736(15)00463-8

    Article  Google Scholar 

  2. Tan Z, Qiu J, Zhang Y, Yang Q, Yin X, Li J, Liu G, Li H, Yang G (2021) Tetramethylpyrazine alleviates behavioral and psychological symptoms of dementia through facilitating hippocampal synaptic plasticity in rats with chronic cerebral hypoperfusion. Front Neurosci 15:646537. https://doi.org/10.3389/fnins.2021.646537

    Article  PubMed  PubMed Central  Google Scholar 

  3. Savulich G, O’Brien JT, Sahakian BJ (2020) Are neuropsychiatric symptoms modifiable risk factors for cognitive decline in Alzheimer’s disease and vascular dementia? The British journal of psychiatry : the journal of mental science 216(1):1–3. https://doi.org/10.1192/bjp.2019.98

    Article  Google Scholar 

  4. Brodaty H, Arasaratnam C (2012) Meta-analysis of nonpharmacological interventions for neuropsychiatric symptoms of dementia. Am J Psychiatry 169(9):946–953. https://doi.org/10.1176/appi.ajp.2012.11101529

    Article  PubMed  Google Scholar 

  5. Park JM, Kim YJ (2019) Effect of ghrelin on memory impairment in a rat model of vascular dementia. J Korean Acad Nurs 49(3):317–328. https://doi.org/10.4040/jkan.2019.49.3.317

    Article  PubMed  Google Scholar 

  6. Liu Q, Bhuiyan MIH, Liu R, Song S, Begum G, Young CB, Foley LM, Chen F, Hitchens TK, Cao G, Chattopadhyay A, He L, Sun D (2021) Attenuating vascular stenosis-induced astrogliosis preserves white matter integrity and cognitive function. J Neuroinflammation 18(1):187. https://doi.org/10.1186/s12974-021-02234-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sigfridsson E, Marangoni M, Hardingham GE, Horsburgh K, Fowler JH (2020) Deficiency of Nrf2 exacerbates white matter damage and microglia/macrophage levels in a mouse model of vascular cognitive impairment. J Neuroinflammation 17(1):367. https://doi.org/10.1186/s12974-020-02038-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kavroulakis E, Simos PG, Kalaitzakis G, Maris TG, Karageorgou D, Zaganas I, Panagiotakis S, Basta M, Vgontzas A, Papadaki E (2018) Myelin content changes in probable Alzheimer’s disease and mild cognitive impairment: associations with age and severity of neuropsychiatric impairment. Journal of magnetic resonance imaging : JMRI 47(5):1359–1372. https://doi.org/10.1002/jmri.25849

    Article  PubMed  Google Scholar 

  9. Benedict RH, Bobholz JH (2007) Multiple sclerosis. Seminars in Neurology 27 (1):78-85. https://doi.org/10.1055/s-2006-956758

  10. Fan H, Tang HB, Shan LQ, Liu SC, Huang DG, Chen X, Chen Z, Yang M, Yin XH, Yang H, Hao DJ (2019) Quercetin prevents necroptosis of oligodendrocytes by inhibiting macrophages/microglia polarization to M1 phenotype after spinal cord injury in rats. J Neuroinflammation 16(1):206. https://doi.org/10.1186/s12974-019-1613-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Xu D, Hu MJ, Wang YQ, Cui YL (2019) Antioxidant activities of quercetin and its complexes for medicinal application. Molecules (Basel, Switzerland) 24 (6). https://doi.org/10.3390/molecules24061123

  12. Tang SM, Deng XT, Zhou J, Li QP, Ge XX, Miao L (2020) Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 121:109604. https://doi.org/10.1016/j.biopha.2019.109604

  13. Spagnuolo C, Moccia S, Russo GL (2018) Anti-inflammatory effects of flavonoids in neurodegenerative disorders. Eur J Med Chem 153:105–115. https://doi.org/10.1016/j.ejmech.2017.09.001

    Article  CAS  PubMed  Google Scholar 

  14. Sun Y, Li C, Li Z, Shangguan A, Jiang J, Zeng W, Zhang S, He Q (2021) Quercetin as an antiviral agent inhibits the Pseudorabies virus in vitro and in vivo. Virus Res 305:198556. https://doi.org/10.1016/j.virusres.2021.198556

    Article  CAS  PubMed  Google Scholar 

  15. Ghosh A, Sarkar S, Mandal AK, Das N (2013) Neuroprotective role of nanoencapsulated quercetin in combating ischemia-reperfusion induced neuronal damage in young and aged rats. PLoS ONE 8(4):e57735. https://doi.org/10.1371/journal.pone.0057735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ansari MA, Abdul HM, Joshi G, Opii WO, Butterfield DA (2009) Protective effect of quercetin in primary neurons against Abeta(1–42): relevance to Alzheimer’s disease. J Nutr Biochem 20(4):269–275. https://doi.org/10.1016/j.jnutbio.2008.03.002

    Article  CAS  PubMed  Google Scholar 

  17. Naeimi R, Baradaran S, Ashrafpour M, Moghadamnia AA, Ghasemi-Kasman M (2018) Querectin improves myelin repair of optic chiasm in lyolecithin-induced focal demyelination model. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 101:485–493. https://doi.org/10.1016/j.biopha.2018.02.125

  18. Ahmad A, Khan MM, Hoda MN, Raza SS, Khan MB, Javed H, Ishrat T, Ashafaq M, Ahmad ME, Safhi MM, Islam F (2011) Quercetin protects against oxidative stress associated damages in a rat model of transient focal cerebral ischemia and reperfusion. Neurochem Res 36(8):1360–1371. https://doi.org/10.1007/s11064-011-0458-6

    Article  CAS  PubMed  Google Scholar 

  19. Zhang J, Ning L, Wang J (2020) Dietary quercetin attenuates depressive-like behaviors by inhibiting astrocyte reactivation in response to stress. Biochem Biophys Res Commun 533(4):1338–1346. https://doi.org/10.1016/j.bbrc.2020.10.016

    Article  CAS  PubMed  Google Scholar 

  20. Yuan Z, Yao F, Hu Z, Sun S, Wu B (2015) Quercetin inhibits the migration and proliferation of astrocytes in wound healing. NeuroReport 26(7):387–393. https://doi.org/10.1097/wnr.0000000000000352

    Article  CAS  PubMed  Google Scholar 

  21. Wang XQ, Yao RQ, Liu X, Huang JJ, Qi DS, Yang LH (2011) Quercetin protects oligodendrocyte precursor cells from oxygen/glucose deprivation injury in vitro via the activation of the PI3K/Akt signaling pathway. Brain Res Bull 86(3–4):277–284. https://doi.org/10.1016/j.brainresbull.2011.07.014

    Article  CAS  PubMed  Google Scholar 

  22. Wu X, Qu X, Zhang Q, Dong F, Yu H, Yan C, Qi D, Wang M, Liu X, Yao R (2014) Quercetin promotes proliferation and differentiation of oligodendrocyte precursor cells after oxygen/glucose deprivation-induced injury. Cell Mol Neurobiol 34(3):463–471. https://doi.org/10.1007/s10571-014-0030-4

    Article  CAS  PubMed  Google Scholar 

  23. Beckmann DV, Carvalho FB, Mazzanti CM, Dos Santos RP, Andrades AO, Aiello G, Rippilinger A, Graça DL, Abdalla FH, Oliveira LS, Gutierres JM, Schetinger MR, Mazzanti A (2014) Neuroprotective role of quercetin in locomotor activities and cholinergic neurotransmission in rats experimentally demyelinated with ethidium bromide. Life Sci 103(2):79–87. https://doi.org/10.1016/j.lfs.2014.03.033

    Article  CAS  PubMed  Google Scholar 

  24. Muir J, Lopez J, Bagot RC (2019) Wiring the depressed brain: optogenetic and chemogenetic circuit interrogation in animal models of depression. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 44(6):1013–1026. https://doi.org/10.1038/s41386-018-0291-6

    Article  Google Scholar 

  25. Haukvik UK, Tamnes CK, Söderman E, Agartz I (2018) Neuroimaging hippocampal subfields in schizophrenia and bipolar disorder: a systematic review and meta-analysis. J Psychiatr Res 104:217–226. https://doi.org/10.1016/j.jpsychires.2018.08.012

    Article  PubMed  Google Scholar 

  26. An L, Shen Y, Chopp M, Zacharek A, Venkat P, Chen Z, Li W, Qian Y, Landschoot-Ward J, Chen J (2021) Deficiency of endothelial nitric oxide synthase (eNOS) exacerbates brain damage and cognitive deficit in a mouse model of vascular dementia. Aging Dis 12(3):732–746. https://doi.org/10.14336/ad.2020.0523

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kim KJ, Diaz JR, Presa JL, Muller PR, Brands MW, Khan MB, Hess DC, Althammer F, Stern JE, Filosa JA (2021) Decreased parenchymal arteriolar tone uncouples vessel-to-neuronal communication in a mouse model of vascular cognitive impairment. GeroScience 43(3):1405–1422. https://doi.org/10.1007/s11357-020-00305-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wang M, Qin C, Luo X, Wang J, Wang X, Xie M, Hu J, Cao J, Hu T, Goldman SA, Nedergaard M, Wang W (2019) Astrocytic connexin 43 potentiates myelin injury in ischemic white matter disease. Theranostics 9(15):4474–4493. https://doi.org/10.7150/thno.31942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tian P, Zhu H, Qian X, Chen Y, Wang Z, Zhao J, Zhang H, Wang G, Chen W (2021) Consumption of butylated starch alleviates the chronic restraint stress-induced neurobehavioral and gut barrier deficits through reshaping the gut microbiota. Front Immunol 12:755481. https://doi.org/10.3389/fimmu.2021.755481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Han X, Xu T, Fang Q, Zhang H, Yue L, Hu G, Sun L (2021) Quercetin hinders microglial activation to alleviate neurotoxicity via the interplay between NLRP3 inflammasome and mitophagy. Redox Biol 44:102010. https://doi.org/10.1016/j.redox.2021.102010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Liu B, Kou J, Li F, Huo D, Xu J, Zhou X, Meng D, Ghulam M, Artyom B, Gao X, Ma N, Han D (2020) Lemon essential oil ameliorates age-associated cognitive dysfunction via modulating hippocampal synaptic density and inhibiting acetylcholinesterase. Aging 12(9):8622–8639. https://doi.org/10.18632/aging.103179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Higaki A, Mogi M, Iwanami J, Min LJ, Bai HY, Shan BS, Kukida M, Kan-No H, Ikeda S, Higaki J, Horiuchi M (2018) Predicting outcome of Morris water maze test in vascular dementia mouse model with deep learning. PLoS ONE 13(2):e0191708. https://doi.org/10.1371/journal.pone.0191708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhang Z, Qin P, Deng Y, Ma Z, Guo H, Guo H, Hou Y, Wang S, Zou W, Sun Y, Ma Y, Hou W (2018) The novel estrogenic receptor GPR30 alleviates ischemic injury by inhibiting TLR4-mediated microglial inflammation. J Neuroinflammation 15(1):206. https://doi.org/10.1186/s12974-018-1246-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ji J, Wang J, Yang J, Wang XP, Huang JJ, Xue TF, Sun XL (2019) The Intra-nuclear SphK2-S1P axis facilitates M1-to-M2 shift of microglia via suppressing HDAC1-mediated KLF4 deacetylation. Front Immunol 10:1241. https://doi.org/10.3389/fimmu.2019.01241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Rawji KS, Young AMH, Ghosh T, Michaels NJ, Mirzaei R, Kappen J, Kolehmainen KL, Alaeiilkhchi N, Lozinski B, Mishra MK, Pu A, Tang W, Zein S, Kaushik DK, Keough MB, Plemel JR, Calvert F, Knights AJ, Gaffney DJ, Tetzlaff W, Franklin RJM, Yong VW (2020) Niacin-mediated rejuvenation of macrophage/microglia enhances remyelination of the aging central nervous system. Acta Neuropathol 139(5):893–909. https://doi.org/10.1007/s00401-020-02129-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Maas DA, Eijsink VD, Spoelder M, van Hulten JA, De Weerd P, Homberg JR, Vallès A, Nait-Oumesmar B, Martens GJM (2020) Interneuron hypomyelination is associated with cognitive inflexibility in a rat model of schizophrenia. Nat Commun 11(1):2329. https://doi.org/10.1038/s41467-020-16218-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Holland PR, Bastin ME, Jansen MA, Merrifield GD, Coltman RB, Scott F, Nowers H, Khallout K, Marshall I, Wardlaw JM, Deary IJ, McCulloch J, Horsburgh K (2011) MRI is a sensitive marker of subtle white matter pathology in hypoperfused mice. Neurobiol Aging 32(12):2325.e2321-2326. https://doi.org/10.1016/j.neurobiolaging.2010.11.009

    Article  Google Scholar 

  38. Chomiak T, Hu B (2009) What is the optimal value of the g-ratio for myelinated fibers in the rat CNS? A theoretical approach. PloS one 4(11):e7754. https://doi.org/10.1371/journal.pone.0007754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Le K, Song Z, Deng J, Peng X, Zhang J, Wang L, Zhou L, Bi H, Liao Z, Feng Z (2020) Quercetin alleviates neonatal hypoxic-ischemic brain injury by inhibiting microglia-derived oxidative stress and TLR4-mediated inflammation. Inflammation research : official journal of the European Histamine Research Society [et al] 69(12):1201–1213. https://doi.org/10.1007/s00011-020-01402-5

    Article  CAS  Google Scholar 

  40. Colonna M, Butovsky O (2017) Microglia function in the central nervous system during health and neurodegeneration. Annu Rev Immunol 35:441–468. https://doi.org/10.1146/annurev-immunol-051116-052358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Voet S, Prinz M, van Loo G (2019) Microglia in central nervous system inflammation and multiple sclerosis pathology. Trends Mol Med 25(2):112–123. https://doi.org/10.1016/j.molmed.2018.11.005

    Article  CAS  PubMed  Google Scholar 

  42. Hu X, Leak RK, Shi Y, Suenaga J, Gao Y, Zheng P, Chen J (2015) Microglial and macrophage polarization—new prospects for brain repair. Nat Rev Neurol 11(1):56–64. https://doi.org/10.1038/nrneurol.2014.207

    Article  PubMed  Google Scholar 

  43. Smith DR, Dumont CM, Park J, Ciciriello AJ, Guo A, Tatineni R, Cummings BJ, Anderson AJ, Shea LD (2020) Polycistronic Delivery of IL-10 and NT-3 Promotes oligodendrocyte myelination and functional recovery in a mouse spinal cord injury model. Tissue Eng Part A 26(11–12):672–682. https://doi.org/10.1089/ten.TEA.2019.0321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Domingues HS, Cruz A, Chan JR, Relvas JB, Rubinstein B, Pinto IM (2018) Mechanical plasticity during oligodendrocyte differentiation and myelination. Glia 66(1):5–14. https://doi.org/10.1002/glia.23206

    Article  PubMed  Google Scholar 

  45. Duncombe J, Kitamura A, Hase Y, Ihara M, Kalaria RN, Horsburgh K (2017) Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia. Clinical science (London, England : 1979) 131 (19):2451–2468. doi:https://doi.org/10.1042/cs20160727

  46. Qin C, Fan WH, Liu Q, Shang K, Murugan M, Wu LJ, Wang W, Tian DS (2017) Fingolimod protects against ischemic white matter damage by modulating microglia toward M2 polarization via STAT3 pathway. Stroke 48(12):3336–3346. https://doi.org/10.1161/strokeaha.117.018505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Fadda G, Armangue T, Hacohen Y, Chitnis T, Banwell B (2021) Paediatric multiple sclerosis and antibody-associated demyelination: clinical, imaging, and biological considerations for diagnosis and care. The Lancet Neurology 20(2):136–149. https://doi.org/10.1016/s1474-4422(20)30432-4

    Article  CAS  PubMed  Google Scholar 

  48. Uemura MT, Maki T, Ihara M, Lee VMY, Trojanowski JQ (2020) Brain microvascular pericytes in vascular cognitive impairment and dementia. Frontiers in aging neuroscience 12:80. https://doi.org/10.3389/fnagi.2020.00080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Yao Y, Han DD, Zhang T, Yang Z (2010) Quercetin improves cognitive deficits in rats with chronic cerebral ischemia and inhibits voltage-dependent sodium channels in hippocampal CA1 pyramidal neurons. Phytotherapy research : PTR 24(1):136–140. https://doi.org/10.1002/ptr.2902

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by grants from Wuhan Science and Technology Plan Application Foundation Frontier Project (2020020601012244).

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Author notes

  1. Zihu Tan, Guang Yang and Jing Qiu contributed equally to this article.

Authors and Affiliations

  1. Department of Geriatrics, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, China

    Zihu Tan, Guang Yang, Jing Qiu, Yu Liu & Nan Shan

  2. Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, 430061, China

    Zihu Tan, Guang Yang, Jing Qiu, Yu Liu & Nan Shan

  3. Hubei Provincial Academy of Traditional Chinese Medicine, 430061, Wuhan, Hubei, People’s Republic of China

    Zihu Tan, Guang Yang, Jing Qiu, Yu Liu & Nan Shan

  4. Clinical College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, 430061, China

    Wenjing Yan & Zhengling Ma

  5. College of Acupuncture and Orthopedics, Hubei University of Chinese Medicine/Hubei Provincial Collaborative Innovation Center of Preventive Treatment By Acupuncture and Moxibustion, Wuhan, 430061, China

    Jia Li & Jing Liu

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  1. Zihu Tan
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Contributions

Z.H.T. performed most of the experiments. G.Y. and J.Q. analyzed the results. J.Q. and W.J.Y. edited figures. J.Q. and Y.L. performed mice BCAS model and statistical analysis. G.Y. and Z.L.M. performed cell culture and treatments. G.Y. and J.L. performed immunoblotting and immunostaining. Z.H.T. wrote preliminary draft of the manuscript. N.S. edited the manuscript. N.S. and Z.H.T. designed experiments and revised the manuscript. All authors approved final version of the manuscript.

Corresponding author

Correspondence to Nan Shan.

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This work was approved by Ethics Committee of Hubei Provincial Hospital of Traditional Chinese Medicine (approval no. HBZY2020-C47-01), and all experimental procedures were performed according to the Chinese Animal Welfare Legislation for protection of animals used for scientific purposes.

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Tan, Z., Yang, G., Qiu, J. et al. Quercetin Alleviates Demyelination Through Regulating Microglial Phenotype Transformation to Mitigate Neuropsychiatric Symptoms in Mice with Vascular Dementia. Mol Neurobiol 59, 3140–3158 (2022). https://doi.org/10.1007/s12035-021-02712-3

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