Skip to main content

Advertisement

SpringerLink
Log in

An Adequate Supply of Bis(ethylmaltolato)oxidovanadium(IV) Remarkably Reversed the Pathological Hallmarks of Alzheimer’s Disease in Triple-Transgenic Middle-Aged Mice

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Alzheimer’s disease (AD) is a complex and progressive neurodegenerative disease with impaired synapse, imbalanced mineral metabolism, protein mis-folding and aggregation. Bis(ethylmaltolato)oxidovanadium(IV) (BEOV), an organic bioactive vanadium compound with low toxicity and high bioavailability, has been studied as therapeutic agent against tuberculosis and diabetes. However, its neuroprotective effects have rarely been reported. Therefore, in this study, the potential application of BEOV in intervening AD cognitive dysfunction and neuropathology was evaluated. Both low- and high-dose of BEOV (0.2 mmol/L and 1.0 mmol/L) supplementation for 2 months improved the spatial learning and memory deficits of the triple-transgenic AD (3 × Tg AD) mice and mitigated the loss of synaptic proteins and synaptic dysfunction. By inhibiting the expression of amyloid-β precursor protein and β-secretase, and the phosphorylation of tau protein at Ser262, Ser396, Ser404, and Ser202/Thr205 residues, BEOV reduced the amyloid-β deposition and neurofibrillary tangle formation in AD mouse brains and primarily cultured neurons. Further analysis of the brain ionome revealed that BEOV supplementation could significantly affect the concentrations of a variety of metals, most of which, including several AD risk metals, showed reduced levels, particularly with a high-dose intake. Additionally, the elemental correlation network identified both conserved and specific elemental correlations, implying a highly complex and dynamic crosstalk between vanadium and other elements during long-term BEOV supplementation. Overall, our results suggest that BEOV is effective in AD intervention via both ameliorating the disease related pathology and regulating metal homeostasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data Availability

The data used to support the findings are all included in the article.

References

  1. Murphy MP (2018) Amyloid-beta solubility in the treatment of Alzheimer’s disease. N Engl J Med 378(4):391–392. https://doi.org/10.1056/NEJMe1714638

    Article  PubMed  Google Scholar 

  2. Honig LS, Vellas B, Woodward M, Boada M, Bullock R, Borrie M et al (2018) Trial of solanezumab for mild dementia due to Alzheimer’s disease. N Engl J Med 378(4):321–330. https://doi.org/10.1056/NEJMoa1705971

    Article  CAS  PubMed  Google Scholar 

  3. Jin N, Zhu H, Liang X, Huang W, Xie Q, Xiao P et al (2017) Sodium selenate activated Wnt/beta-catenin signaling and repressed amyloid-beta formation in a triple transgenic mouse model of Alzheimer’s disease. Exp Neurol 297:36–49. https://doi.org/10.1016/j.expneurol.2017.07.006

    Article  CAS  PubMed  Google Scholar 

  4. Selkoe DJ (2004) Cell biology of protein misfolding: the examples of Alzheimer’s and Parkinson’s diseases. Nat Cell Biol 6(11):1054–1061. https://doi.org/10.1038/ncb1104-1054

    Article  CAS  PubMed  Google Scholar 

  5. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A 82(12):4245–4249. https://doi.org/10.1073/pnas.82.12.4245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Cope TE, Rittman T, Borchert RJ, Jones PS, Vatansever D, Allinson K et al (2018) Tau burden and the functional connectome in Alzheimer’s disease and progressive supranuclear palsy. Brain 141(2):550–567. https://doi.org/10.1093/brain/awx347

    Article  PubMed  PubMed Central  Google Scholar 

  7. Nisbet RM, Polanco JC, Ittner LM, Gotz J (2015) Tau aggregation and its interplay with amyloid-beta. Acta Neuropathol 129(2):207–220. https://doi.org/10.1007/s00401-014-1371-2

    Article  CAS  PubMed  Google Scholar 

  8. Ballatore C, Lee VM, Trojanowski JQ (2007) Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci 8(9):663–672. https://doi.org/10.1038/nrn2194

    Article  CAS  PubMed  Google Scholar 

  9. Dong Y, Stewart T, Zhang Y, Shi M, Tan C, Li X et al (2019) Anti-diabetic vanadyl complexes reduced Alzheimer’s disease pathology independent of amyloid plaque deposition. Sci China Life Sci 62(1):126–139. https://doi.org/10.1007/s11427-018-9350-1

    Article  CAS  PubMed  Google Scholar 

  10. Paglia G, Miedico O, Cristofano A, Vitale M, Angiolillo A, Chiaravalle AE et al (2016) Distinctive pattern of serum elements during the progression of Alzheimer’s disease. Sci Rep 6:22769. https://doi.org/10.1038/srep22769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gonzalez-Dominguez R, Garcia-Barrera T, Gomez-Ariza JL (2014) Characterization of metal profiles in serum during the progression of Alzheimer’s disease. Metallomics 6(2):292–300. https://doi.org/10.1039/c3mt00301a

    Article  CAS  PubMed  Google Scholar 

  12. Gerhardsson L, Lundh T, Minthon L, Londos E (2008) Metal concentrations in plasma and cerebrospinal fluid in patients with Alzheimer’s disease. Dement Geriatr Cogn Disord 25(6):508–515. https://doi.org/10.1159/000129365

    Article  CAS  PubMed  Google Scholar 

  13. Szabo ST, Harry GJ, Hayden KM, Szabo DT, Birnbaum L (2016) Comparison of metal levels between postmortem brain and ventricular fluid in Alzheimer’s disease and nondemented elderly controls. Toxicol Sci 150(2):292–300. https://doi.org/10.1093/toxsci/kfv325

    Article  CAS  PubMed  Google Scholar 

  14. Adam AMA, Naglah AM, Al-Omar MA, Refat MS (2017) Synthesis of a new insulin-mimetic anti-diabetic drug containing vitamin A and vanadium(IV) salt: Chemico-biological characterizations. Int J Immunopathol Pharmacol 30(3):272–281. https://doi.org/10.1177/0394632017719601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Niu X, Xiao R, Wang N, Wang Z, Zhang Y, Xia Q et al (2016) The molecular mechanisms and rational design of anti-diabetic vanadium compounds. Curr Top Med Chem 16(8):811–822. https://doi.org/10.2174/1568026615666150827094652

    Article  CAS  PubMed  Google Scholar 

  16. Sanna D, Ugone V, Serra M, Garribba E (2017) Speciation of potential anti-diabetic vanadium complexes in real serum samples. J Inorg Biochem 173:52–65. https://doi.org/10.1016/j.jinorgbio.2017.04.023

    Article  CAS  PubMed  Google Scholar 

  17. Thompson KH, Orvig C (2006) Vanadium in diabetes: 100 years from phase 0 to phase I. J Inorg Biochem 100(12):1925–1935. https://doi.org/10.1016/j.jinorgbio.2006.08.016

    Article  CAS  PubMed  Google Scholar 

  18. Gao Z, Zhang C, Yu S, Yang X, Wang K (2011) Vanadyl bisacetylacetonate protects beta cells from palmitate-induced cell death through the unfolded protein response pathway. J Biol Inorg Chem 16(5):789–798. https://doi.org/10.1007/s00775-011-0780-0

    Article  CAS  PubMed  Google Scholar 

  19. Zhao P, Yang X (2013) Vanadium compounds modulate PPARgamma activity primarily by increasing PPARgamma protein levels in mouse insulinoma NIT-1 cells. Metallomics 5(7):836–843. https://doi.org/10.1039/c3mt20249f

    Article  CAS  PubMed  Google Scholar 

  20. Wu Y, Huang M, Zhao P, Yang X (2013) Vanadyl acetylacetonate upregulates PPARgamma and adiponectin expression in differentiated rat adipocytes. J Biol Inorg Chem 18(6):623–631. https://doi.org/10.1007/s00775-013-1007-3

    Article  CAS  PubMed  Google Scholar 

  21. Irving E, Stoker AW (2017) Vanadium Compounds as PTP Inhibitors. Molecules 22(12) https://doi.org/10.3390/molecules22122269.

  22. McLauchlan CC, Hooker JD, Jones MA, Dymon Z, Backhus EA, Greiner BA et al (2010) Inhibition of acid, alkaline, and tyrosine (PTP1B) phosphatases by novel vanadium complexes. J Inorg Biochem 104(3):274–281. https://doi.org/10.1016/j.jinorgbio.2009.12.001

    Article  CAS  PubMed  Google Scholar 

  23. Rajala RV, Basavarajappa DK, Dighe R, Rajala A (2013) Spatial and temporal aspects and the interplay of Grb14 and protein tyrosine phosphatase-1B on the insulin receptor phosphorylation. Cell Commun Signal 11:96. https://doi.org/10.1186/1478-811x-11-96

    Article  PubMed  PubMed Central  Google Scholar 

  24. He Z, Han S, Wu C, Liu L, Zhu H, Liu A et al (2020) Bis(ethylmaltolato)oxidovanadium(iv) inhibited the pathogenesis of Alzheimer’s disease in triple transgenic model mice. Metallomics 12(4):474–490. https://doi.org/10.1039/c9mt00271e

    Article  CAS  PubMed  Google Scholar 

  25. Zheng L, Zhu HZ, Wang BT, Zhao QH, Du XB, Zheng Y et al (2016) Sodium selenate regulates the brain ionome in a transgenic mouse model of Alzheimer’s disease. Sci Rep 6:39290. https://doi.org/10.1038/srep39290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Vorhees CV, Williams MT (2006) Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc 1(2):848–858. https://doi.org/10.1038/nprot.2006.116

    Article  PubMed  PubMed Central  Google Scholar 

  27. Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11(1):47–60. https://doi.org/10.1016/0165-0270(84)90007-4

    Article  CAS  PubMed  Google Scholar 

  28. Lins N, Mourão L, Trévia N, Passos A, Farias JA, Assunção J et al (2016) Virus infections on prion diseased mice exacerbate inflammatory microglial response. Oxid Med Cell Longev 2016:3974648. https://doi.org/10.1155/2016/3974648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Derecki NC, Cronk JC, Lu Z, Xu E, Abbott SB, Guyenet PG et al (2012) Wild-type microglia arrest pathology in a mouse model of Rett syndrome. Nature 484(7392):105–109. https://doi.org/10.1038/nature10907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gallyas F (1971) Silver staining of Alzheimer’s neurofibrillary changes by means of physical development. Acta Morphol Acad Sci Hung 19(1):1–8

    CAS  PubMed  Google Scholar 

  31. Efstathiou CE (2006) Estimation of type I error probability from experimental Dixon’s “Q” parameter on testing for outliers within small size data sets. Talanta 69(5):1068–1071. https://doi.org/10.1016/j.talanta.2005.12.031

    Article  CAS  PubMed  Google Scholar 

  32. Villasenor Alva JA, Estrada EG (2009) A generalization of Shapiro–Wilk’s test for multivariate normality. Communications in Statistics - Theory and Methods 38(11):1870–1883. https://doi.org/10.1080/03610920802474465

    Article  Google Scholar 

  33. Terry RD, Masliah E, Salmon DP, Butters N, DeTeresa R, Hill R et al (1991) Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30(4):572–580. https://doi.org/10.1002/ana.410300410

    Article  CAS  PubMed  Google Scholar 

  34. DeKosky ST, Scheff SW (1990) Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann Neurol 27(5):457–464. https://doi.org/10.1002/ana.410270502

    Article  CAS  PubMed  Google Scholar 

  35. Palop JJ, Mucke L (2010) Amyloid-beta-induced neuronal dysfunction in Alzheimer’s disease: from synapses toward neural networks. Nat Neurosci 13(7):812–818. https://doi.org/10.1038/nn.2583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Li Q, Südhof TC (2004) Cleavage of amyloid-beta precursor protein and amyloid-beta precursor-like protein by BACE 1. J Biol Chem 279(11):10542–10550. https://doi.org/10.1074/jbc.M310001200

    Article  CAS  PubMed  Google Scholar 

  37. Hogl S, Kuhn PH, Colombo A, Lichtenthaler SF (2011) Determination of the proteolytic cleavage sites of the amyloid precursor-like protein 2 by the proteases ADAM10, BACE1 and γ-secretase. PLoS ONE 6(6):e21337. https://doi.org/10.1371/journal.pone.0021337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Xie Y, Tan Y, Zheng Y, Du X, Liu Q (2017) Ebselen ameliorates beta-amyloid pathology, tau pathology, and cognitive impairment in triple-transgenic Alzheimer’s disease mice. J Biol Inorg Chem 22(6):851–865. https://doi.org/10.1007/s00775-017-1463-2

    Article  CAS  PubMed  Google Scholar 

  39. Choo XY, Alukaidey L, White AR, Grubman A (2013) Neuroinflammation and copper in Alzheimer’s disease. Int J Alzheimers Dis 2013:145345. https://doi.org/10.1155/2013/145345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Mao X, Ye J, Zhou S, Pi R, Dou J, Zang L et al (2012) The effects of chronic copper exposure on the amyloid protein metabolisim associated genes’ expression in chronic cerebral hypoperfused rats. Neurosci Lett 518(1):14–18. https://doi.org/10.1016/j.neulet.2012.04.030

    Article  CAS  PubMed  Google Scholar 

  41. Rembach A, Hare DJ, Lind M, Fowler CJ, Cherny RA, McLean C et al (2013) Decreased copper in Alzheimer’s disease brain is predominantly in the soluble extractable fraction. Int J Alzheimers Dis 2013:623241. https://doi.org/10.1155/2013/623241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Mathys ZK, White AR (2017) Copper and Alzheimer’s Disease Adv Neurobiol 18:199–216. https://doi.org/10.1007/978-3-319-60189-2_10

    Article  PubMed  Google Scholar 

  43. Belaidi AA, Bush AI (2016) Iron neurochemistry in Alzheimer’s disease and Parkinson’s disease: targets for therapeutics. J Neurochem 139(Suppl 1):179–197. https://doi.org/10.1111/jnc.13425

    Article  CAS  PubMed  Google Scholar 

  44. Kozlov S, Afonin A, Evsyukov I, Bondarenko A (2017) Alzheimer’s disease: as it was in the beginning. Rev Neurosci 28(8):825–843. https://doi.org/10.1515/revneuro-2017-0006

    Article  CAS  PubMed  Google Scholar 

  45. Telling ND, Everett J, Collingwood JF, Dobson J, van der Laan G, Gallagher JJ et al (2017) Iron biochemistry is correlated with amyloid plaque morphology in an established mouse model of Alzheimer’s disease. Cell Chem Biol 24(10):1205-1215.e1203. https://doi.org/10.1016/j.chembiol.2017.07.014

    Article  CAS  PubMed  Google Scholar 

  46. Alzheimer A, Stelzmann RA, Schnitzlein HN, Murtagh FR (1995) An English translation of Alzheimer’s 1907 paper, “Uber eine eigenartige Erkankung der Hirnrinde.” Clin Anat 8(6):429–431. https://doi.org/10.1002/ca.980080612

    Article  CAS  PubMed  Google Scholar 

  47. Shioda N, Morioka M, Fukunaga K (2008) Vanadium compounds enhance adult neurogenesis after brain ischemia. Yakugaku Zasshi 128(3):413–417. https://doi.org/10.1248/yakushi.128.413

    Article  CAS  PubMed  Google Scholar 

  48. Luchsinger JA (2012) Type 2 diabetes and cognitive impairment: linking mechanisms. J Alzheimers Dis 30 Suppl 2(0):S185–198

  49. Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA (2004) Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol 61(5):661–666. https://doi.org/10.1001/archneur.61.5.661

    Article  PubMed  Google Scholar 

  50. Grodstein F, Chen J, Wilson RS, Manson JE (2001) Type 2 diabetes and cognitive function in community-dwelling elderly women. Diabetes Care 24(6):1060–1065. https://doi.org/10.2337/diacare.24.6.1060

    Article  CAS  PubMed  Google Scholar 

  51. Lithner F (1996) Diabetes mellitus and Alzheimer’s disease. Diabetologia 39(10):1242. https://doi.org/10.1007/bf02658517

    Article  CAS  PubMed  Google Scholar 

  52. Chatterjee S, Peters SA, Woodward M, Mejia Arango S, Batty GD, Beckett N et al (2016) Type 2 diabetes as a risk factor for dementia in women compared with men: a pooled analysis of 2.3 million people comprising more than 100,000 cases of dementia. Diabetes Care 39(2):300–307. https://doi.org/10.2337/dc15-1588

    Article  CAS  PubMed  Google Scholar 

  53. De Felice FG, Vieira MN, Bomfim TR, Decker H, Velasco PT, Lambert MP et al (2009) Protection of synapses against Alzheimer’s-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers. Proc Natl Acad Sci U S A 106(6):1971–1976. https://doi.org/10.1073/pnas.0809158106

    Article  PubMed  PubMed Central  Google Scholar 

  54. Rickle A, Bogdanovic N, Volkman I, Winblad B, Ravid R, Cowburn RF (2004) Akt activity in Alzheimer’s disease and other neurodegenerative disorders. NeuroReport 15(6):955–959. https://doi.org/10.1097/00001756-200404290-00005

    Article  CAS  PubMed  Google Scholar 

  55. Griffin RJ, Moloney A, Kelliher M, Johnston JA, Ravid R, Dockery P et al (2005) Activation of Akt/PKB, increased phosphorylation of Akt substrates and loss and altered distribution of Akt and PTEN are features of Alzheimer’s disease pathology. J Neurochem 93(1):105–117. https://doi.org/10.1111/j.1471-4159.2004.02949.x

    Article  CAS  PubMed  Google Scholar 

  56. Thompson KH, Lichter J, LeBel C, Scaife MC, McNeill JH, Orvig C (2009) Vanadium treatment of type 2 diabetes: a view to the future. J Inorg Biochem 103(4):554–558. https://doi.org/10.1016/j.jinorgbio.2008.12.003

    Article  CAS  PubMed  Google Scholar 

  57. Lue LF, Kuo YM, Roher AE, Brachova L, Shen Y, Sue L et al (1999) Soluble amyloid beta peptide concentration as a predictor of synaptic change in Alzheimer’s disease. Am J Pathol 155(3):853–862. https://doi.org/10.1016/s0002-9440(10)65184-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Puzzo D, Privitera L, Leznik E, Fà M, Staniszewski A, Palmeri A et al (2008) Picomolar amyloid-beta positively modulates synaptic plasticity and memory in hippocampus. J Neurosci 28(53):14537–14545. https://doi.org/10.1523/jneurosci.2692-08.2008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Handoko M, Grant M, Kuskowski M, Zahs KR, Wallin A, Blennow K et al (2013) Correlation of specific amyloid-β oligomers with tau in cerebrospinal fluid from cognitively normal older adults. JAMA Neurol 70(5):594–599. https://doi.org/10.1001/jamaneurol.2013.48

    Article  PubMed  PubMed Central  Google Scholar 

  60. DaRocha-Souto B, Scotton TC, Coma M, Serrano-Pozo A, Hashimoto T, Serenó L et al (2011) Brain oligomeric β-amyloid but not total amyloid plaque burden correlates with neuronal loss and astrocyte inflammatory response in amyloid precursor protein/tau transgenic mice. J Neuropathol Exp Neurol 70(5):360–376. https://doi.org/10.1097/NEN.0b013e318217a118

    Article  CAS  PubMed  Google Scholar 

  61. Cao G, Su P, Zhang S, Guo L, Zhang H, Liang Y et al (2016) Ginsenoside Re reduces Aβ production by activating PPARγ to inhibit BACE1 in N2a/APP695 cells. Eur J Pharmacol 793:101–108. https://doi.org/10.1016/j.ejphar.2016.11.006

    Article  CAS  PubMed  Google Scholar 

  62. McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K et al (1999) Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer’s disease. Ann Neurol 46(6):860–866. https://doi.org/10.1002/1531-8249(199912)46:6%3c860::aid-ana8%3e3.0.co;2-m

    Article  CAS  PubMed  Google Scholar 

  63. Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR (1998) Copper, iron and zinc in Alzheimer’s disease senile plaques. J Neurol Sci 158(1):47–52. https://doi.org/10.1016/s0022-510x(98)00092-6

    Article  CAS  PubMed  Google Scholar 

  64. Chen WT, Liao YH, Yu HM, Cheng IH, Chen YR (2011) Distinct effects of Zn2+, Cu2+, Fe3+, and Al3+ on amyloid-beta stability, oligomerization, and aggregation: amyloid-beta destabilization promotes annular protofibril formation. J Biol Chem 286(11):9646–9656. https://doi.org/10.1074/jbc.M110.177246

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Xie Y, Liu Q, Zheng L, Wang B, Qu X, Ni J et al (2018) Se-methylselenocysteine ameliorates neuropathology and cognitive deficits by attenuating oxidative stress and metal dyshomeostasis in Alzheimer model mice. Mol Nutr Food Res 62(12):e1800107. https://doi.org/10.1002/mnfr.201800107

    Article  CAS  PubMed  Google Scholar 

  66. Wang Y, Yang R, Gu J, Yin X, Jin N, Xie S et al (2015) Cross talk between PI3K-AKT-GSK-3beta and PP2A pathways determines tau hyperphosphorylation. Neurobiol Aging 36(1):188–200. https://doi.org/10.1016/j.neurobiolaging.2014.07.035

    Article  CAS  PubMed  Google Scholar 

  67. Li G-P, Jiang L, Ni J-Z, Liu Q, Zhang Y (2014) Computational identification of a new SelD-like family that may participate in sulfur metabolism in hyperthermophilic sulfur-reducing archaea. Bmc Genomics 15 https://doi.org/10.1186/1471-2164-15-908

  68. Shin RW, Kruck TP, Murayama H, Kitamoto T (2003) A novel trivalent cation chelator Feralex dissociates binding of aluminum and iron associated with hyperphosphorylated tau of Alzheimer’s disease. Brain Res 961(1):139–146. https://doi.org/10.1016/s0006-8993(02)03893-3

    Article  CAS  PubMed  Google Scholar 

  69. Sivanesan S, Tan A, Rajadas J (2013) Pathogenesis of Abeta oligomers in synaptic failure. Curr Alzheimer Res 10(3):316–323. https://doi.org/10.2174/1567205011310030011

    Article  CAS  PubMed  Google Scholar 

  70. Han F, Shioda N, Moriguchi S, Qin ZH, Fukunaga K (2008) The vanadium (IV) compound rescues septo-hippocampal cholinergic neurons from neurodegeneration in olfactory bulbectomized mice. Neuroscience 151(3):671–679. https://doi.org/10.1016/j.neuroscience.2007.11.011

    Article  CAS  PubMed  Google Scholar 

  71. Callahan LM, Coleman PD (1995) Neurons bearing neurofibrillary tangles are responsible for selected synaptic deficits in Alzheimer’s disease. Neurobiol Aging 16(3):311–314. https://doi.org/10.1016/0197-4580(95)00035-d

    Article  CAS  PubMed  Google Scholar 

  72. Cook IA, Leuchter AF (1996) Synaptic dysfunction in Alzheimer’s disease: clinical assessment using quantitative EEG. Behav Brain Res 78(1):15–23. https://doi.org/10.1016/0166-4328(95)00214-6

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was financially supported by grants from the National Natural Science Foundation of China (21877081 and 31771407), the Guangdong Provincial Key S&T Program (2018B030336001), the Shenzhen Science and Technology Innovation Commission (JCYJ20200109110001818), and the Shenzhen-Hong Kong Institute of brain Science-Shenzhen Fundamental Research Institutions (2021SHIBS0003). We thank the Instrumental Analysis Center of Shenzhen University (Xili Campus) for providing access to the instruments used in the experiments.

Author information

Authors and Affiliations

  1. Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, 518060, China

    Zhijun He, Lin Zheng, Xiaoqian Li, Bingyu Ren, Nan Li, Jiazuan Ni, Yan Zhang & Qiong Liu

  2. Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, China

    Zhijun He & Jiazuan Ni

  3. Food Inspection & Quarantine Center, Shenzhen Entry-Exit Inspection and Quarantine Bureau, Shenzhen, 518045, China

    Xu Zhao & Qionghui Zhao

  4. National Quality Supervision and Inspection Center for Selenium-Enriched Products, Enshi, 445000, China

    Hua Xue

  5. Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China

    Nan Li, Yan Zhang & Qiong Liu

  6. Shenzhen Bay Laboratory, Shenzhen, 518055, China

    Yan Zhang & Qiong Liu

Authors
  1. Zhijun He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lin Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xu Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaoqian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hua Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qionghui Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bingyu Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jiazuan Ni
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Qiong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

QL and YZ designed the study. ZJH, XZ, QHZ, BYR, and XXL performed the majority of behavioral experiments and analyzed the data. ZJH, HX, LZ, and XXL performed the in vitro experiments and analyzed the data. ZJH, YZ, and LZ co-wrote the manuscript. JZN, NL, and QL contributed in interpreting the results. All authors reviewed and concurred with the final manuscript.

Corresponding authors

Correspondence to Yan Zhang or Qiong Liu.

Ethics declarations

Ethics Approval

Animal experiments were performed in compliance with the institutional guidelines at Shenzhen University. The protocol was approved by the Laboratory Animal Ethics Committee of Shenzhen University (Permit Number: AEWC-20140615–002).

Consent to Participate

All the authors participated as at appropriate to the work.

Consent for Publication

All other authors have read the manuscript and have agreed to submit it in its current form for consideration for publication in the Biological Trace Element Research.

Competing Interests

All authors declare that they have no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Zhijun He and Lin Zheng contribute equally to this work

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 2.20 MB)

Supplementary file2 (XLSX 44.6 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

He, Z., Zheng, L., Zhao, X. et al. An Adequate Supply of Bis(ethylmaltolato)oxidovanadium(IV) Remarkably Reversed the Pathological Hallmarks of Alzheimer’s Disease in Triple-Transgenic Middle-Aged Mice. Biol Trace Elem Res 200, 3248–3264 (2022). https://doi.org/10.1007/s12011-021-02938-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-021-02938-1

Keywords

Search

Navigation