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Cited by 93Trace Elements in HealthHeavy Metal Exposure and ToxicityNeurological diseases and metabolism

Zinc and Central Nervous System Disorders

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Wang, Bangqi, Fang, Tianshu, Chen, Hongping·2023·Nutrients
DOI 10.3390/nu15092140PMC PMC10180555
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Abstract

Zinc (Zn2+) is the second most abundant necessary trace element in the human body, exerting a critical role in many physiological processes such as cellular proliferation, transcription, apoptosis, growth, immunity, and wound healing. It is an essential catalyst ion for many enzymes and transcription factors. The maintenance of Zn2+ homeostasis is essential for the central nervous system, in which Zn2+ is abundantly distributed and accumulates in presynaptic vesicles. Synaptic Zn2+ is necessary for neural transmission, playing a pivotal role in neurogenesis, cognition, memory, and learning. Emerging data suggest that disruption of Zn2+ homeostasis is associated with several central nervous system disorders including Alzheimer’s disease, depression, Parkinson’s disease, multiple sclerosis, schizophrenia, epilepsy, and traumatic brain injury. Here, we reviewed the correlation between Zn2+ and these central nervous system disorders. The potential mechanisms were also included. We hope that this review can provide new clues for the prevention and treatment of nervous system disorders.

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  • Excess zinc promotes Aβ aggregation, while zinc deficiency impairs pro-BDNF maturation, enhancing glutamate excitotoxicity and synaptic vulnerability.

    “Excess zinc promotes Aβ aggregation, while zinc deficiency impairs pro-BDNF maturation, enhancing glutamate excitotoxicity and synaptic vulnerability [112].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [112]

    Section 3.1 states that high zinc concentrations increase fibrillar Aβ aggregation and that zinc-dependent enzymes help mature pro-BDNF. It describes impaired BDNF maturation as a possible mechanism for neuronal death and altered excitability, but attributes glutamatergic overdrive to Aβ sequestering zinc; it does not establish the claimed causal chain from zinc deficiency through impaired maturation to glutamate excitotoxicity and synaptic vulnerability. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Sequestration of zinc and copper within plaques and tangles may cause a functional deficiency in surrounding neuronal milieu, disrupting signaling and plasticity.

    “Importantly, sequestration of zinc and copper within plaques and tangles may also cause a functional deficiency in the surrounding neuronal milieu, disrupting signaling and plasticity [112].”

    From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [112]

    Section 3.1 (page not provided) says Aβ sequesters zinc, depleting zinc-mediated glutamatergic neurotransmission and perturbing long-term potentiation. It does not establish that copper, or zinc and copper within tangles, cause the proposed functional deficiency in the surrounding neuronal milieu. (LLM, conf=0.88)

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  1. [1]Andreini C. Banci L. Bertini I. Rosato A. Counting the zinc-proteins encoded in the human genome J. Proteome Res. 2006 5 196 201 10.1021/pr050361j 16396512 · DOI · Paper page
  2. [2]Vallee B.L. Falchuk K.H. The biochemical basis of zinc physiology Physiol. Rev. 1993 73 79 118 10.1152/physrev.1993.73.1.79 8419966 · DOI
  3. [3]Rink L. Haase H. Zinc homeostasis and immunity Trends Immunol. 2007 28 1 4 10.1016/j.it.2006.11.005 17126599 · DOI
  4. [4]O’Halloran T.V. Transition metals in control of gene expression Science 1993 261 715 725 10.1126/science.8342038 8342038 · DOI
  5. [6]Hambidge M. Human zinc deficiency J. Nutr. 2000 130 1344S 1349S 10.1093/jn/130.5.1344S 10801941 · DOI
  6. [7]Sandstead H.H. Subclinical zinc deficiency impairs human brain function J. Trace Elem. Med. Biol. 2012 26 70 73 10.1016/j.jtemb.2012.04.018 22673824 · DOI
  7. [8]Kawahara M. Tanaka K.I. Kato-Negishi M. Zinc, Carnosine, and Neurodegenerative Diseases Nutrients 2018 10 147 10.3390/nu10020147 29382141 PMC5852723 · DOI · Paper page
  8. [10]Wastney M.E. Aamodt R.L. Rumble W.F. Henkin R.I. Kinetic analysis of zinc metabolism and its regulation in normal humans Am. J. Physiol.-Regul. Integr. Comp. Physiol. 1986 251 R398 R408 10.1152/ajpregu.1986.251.2.R398 3740321 · DOI
  9. [11]Solomons N.W. Update on zinc biology Ann. Nutr. Metab. 2013 62 (Suppl. 1) 8 17 10.1159/000348547 23689109 · DOI
  10. [13]Heintschel M. Heuberger R. The Potential Role of Zinc Supplementation on Pressure Injury Healing in Older Adults: A Review of the Literature Wounds-Compend. Clin. Res. Pract. 2017 29 56 61 28272014
  11. [14]Portbury S.D. Adlard P.A. Zinc Signal in Brain Diseases Int. J. Mol. Sci. 2017 18 2506 10.3390/ijms18122506 29168792 PMC5751109 · DOI
  12. [15]Krall R.F. Tzounopoulos T. Aizenman E. The Function and Regulation of Zinc in the Brain Neuroscience 2021 457 235 258 10.1016/j.neuroscience.2021.01.010 33460731 PMC7897305 · DOI
  13. [16]Nuttall J.R. Oteiza P.I. Zinc and the aging brain Genes Nutr. 2014 9 379 10.1007/s12263-013-0379-x 24366781 PMC3896632 · DOI
  14. [17]Koh J.Y. Zinc and disease of the brain Mol. Neurobiol. 2001 24 99 106 10.1385/MN:24:1-3:099 11831557 · DOI
  15. [18]Szewczyk B. Zinc homeostasis and neurodegenerative disorders Front. Aging Neurosci. 2013 5 33 10.3389/fnagi.2013.00033 23882214 PMC3715721 · DOI · Paper page
  16. [19]Frederickson C.J. Suh S.W. Silva D. Frederickson C.J. Thompson R.B. Importance of zinc in the central nervous system: The zinc-containing neuron J. Nutr. 2000 130 1471S 1483S 10.1093/jn/130.5.1471S 10801962 · DOI
  17. [20]Kumar V. Kumar A. Singh K. Avasthi K. Kim J.J. Neurobiology of zinc and its role in neurogenesis Eur. J. Nutr. 2021 60 55 64 10.1007/s00394-020-02454-3 33399973 · DOI
  18. [21]Smart T.G. Hosie A.M. Miller P.S. Zn2+ ions: Modulators of excitatory and inhibitory synaptic activity Neuroscientist 2004 10 432 442 10.1177/1073858404263463 15359010 · DOI
  19. [22]Westbrook G.L. Mayer M.L. Micromolar concentrations of Zn2+ antagonize NMDA and GABA responses of hippocampal neurons Nature 1987 328 640 643 10.1038/328640a0 3039375 · DOI
  20. [23]Sensi S.L. Yin H.Z. Carriedo S.G. Rao S.S. Weiss J.H. Preferential Zn2+ influx through Ca2+-permeable AMPA/kainate channels triggers prolonged mitochondrial superoxide production Proc. Natl. Acad. Sci. USA 1999 96 2414 2419 10.1073/pnas.96.5.2414 10051656 PMC26798 · DOI · Paper page
  21. [24]Kodirov S.A. Takizawa S. Joseph J. Kandel E.R. Shumyatsky G.P. Bolshakov V.Y. Synaptically released zinc gates long-term potentiation in fear conditioning pathways Proc. Natl. Acad. Sci. USA 2006 103 15218 15223 10.1073/pnas.0607131103 17005717 PMC1622803 · DOI
  22. [25]Takeda A. Nakamura M. Fujii H. Tamano H. Synaptic Zn2+ homeostasis and its significance Metallomics 2013 5 417 423 10.1039/c3mt20269k 23423555 · DOI
  23. [26]Patrick W.H. Dyck R.H. Signaling by Synaptic Zinc is Required for Whisker-Mediated, Fine Texture Discrimination Neuroscience 2018 369 242 247 10.1016/j.neuroscience.2017.11.020 29158108 · DOI
  24. [27]Barr C.A. Burdette S.C. The zinc paradigm for metalloneurochemistry Essays Biochem. 2017 61 225 235 28487399
  25. [28]Takeda A. Tamano H. Tochigi M. Oku N. Zinc homeostasis in the hippocampus of zinc-deficient young adult rats Neurochem. Int. 2005 46 221 225 10.1016/j.neuint.2004.10.003 15670638 · DOI
  26. [29]Choi B.Y. Hong D.K. Jeong J.H. Lee B.E. Koh J.Y. Suh S.W. Zinc transporter 3 modulates cell proliferation and neuronal differentiation in the adult hippocampus Stem Cells 2020 38 994 1006 10.1002/stem.3194 32346941 PMC7496127 · DOI
  27. [30]Keller K.A. Grider A. Coffield J.A. Age-dependent influence of dietary zinc restriction on short-term memory in male rats Physiol. Behav. 2001 72 339 348 10.1016/S0031-9384(00)00421-2 11274675 · DOI
  28. [31]Lee S.R. Critical Role of Zinc as Either an Antioxidant or a Prooxidant in Cellular Systems Oxid. Med. Cell. Longev. 2018 2018 9156285 10.1155/2018/9156285 29743987 PMC5884210 · DOI · Paper page
  29. [32]Tonder N. Johansen F.F. Frederickson C.J. Zimmer J. Diemer N.H. Possible role of zinc in the selective degeneration of dentate hilar neurons after cerebral ischemia in the adult rat Neurosci. Lett. 1990 109 247 252 10.1016/0304-3940(90)90002-Q 2330128 · DOI
  30. [33]Li Y. Hough C.J. Suh S.W. Sarvey J.M. Frederickson C.J. Rapid translocation of Zn2+ from presynaptic terminals into postsynaptic hippocampal neurons after physiological stimulation J. Neurophysiol. 2001 86 2597 2604 10.1152/jn.2001.86.5.2597 11698545 · DOI
  31. [34]Suh S.W. Thompson R.B. Frederickson C.J. Loss of vesicular zinc and appearance of perikaryal zinc after seizures induced by pilocarpine Neuroreport 2001 12 1523 1525 10.1097/00001756-200105250-00044 11388441 · DOI
  32. [35]Li M.S. Adesina S.E. Ellis C.L. Gooch J.L. Hoover R.S. Williams C.R. NADPH oxidase-2 mediates zinc deficiency-induced oxidative stress and kidney damage Am. J. Physiol.-Cell Physiol. 2017 312 C47 C55 10.1152/ajpcell.00208.2016 27806940 PMC5283897 · DOI
  33. [36]Choi S. Hong D.K. Choi B.Y. Suh S.W. Zinc in the Brain: Friend or Foe? Int. J. Mol. Sci. 2020 21 8941 10.3390/ijms21238941 33255662 PMC7728061 · DOI
  34. [37]Maret W. Krezel A. Cellular zinc and redox buffering capacity of metallothionein/thionein in health and disease Mol. Med. 2007 13 371 375 10.2119/2007-00036.Maret 17622324 PMC1952669 · DOI
  35. [38]Quaife C.J. Findley S.D. Erickson J.C. Froelick G.J. Kelly E.J. Zambrowicz B.P. Palmiter R.D. Induction of a new metallothionein isoform (MT-IV) occurs during differentiation of stratified squamous epithelia Biochemistry 1994 33 7250 7259 10.1021/bi00189a029 8003488 · DOI
  36. [39]Manso Y. Adlard P.A. Carrasco J. Vasak M. Hidalgo J. Metallothionein and brain inflammation J. Biol. Inorg. Chem. 2011 16 1103 1113 10.1007/s00775-011-0802-y 21678079 · DOI
  37. [40]Thirumoorthy N. Shyam S.A. Manisenthil K.K. Senthil K.M. Ganesh G. Chatterjee M. A review of metallothionein isoforms and their role in pathophysiology World J. Surg. Oncol. 2011 9 54 10.1186/1477-7819-9-54 21599891 PMC3114003 · DOI
  38. [41]Sato M. Kondoh M. Recent studies on metallothionein: Protection against toxicity of heavy metals and oxygen free radicals Tohoku J. Exp. Med. 2002 196 9 22 10.1620/tjem.196.9 12498322 · DOI
  39. [42]Thingholm T.E. Ronnstrand L. Rosenberg P.A. Why and how to investigate the role of protein phosphorylation in ZIP and ZnT zinc transporter activity and regulation Cell. Mol. Life Sci. 2020 77 3085 3102 10.1007/s00018-020-03473-3 32076742 PMC7391401 · DOI
  40. [43]Palmiter R.D. Findley S.D. Cloning and functional characterization of a mammalian zinc transporter that confers resistance to zinc Embo J. 1995 14 639 649 10.1002/j.1460-2075.1995.tb07042.x 7882967 PMC398127 · DOI
  41. [44]Cole T.B. Robbins C.A. Wenzel H.J. Schwartzkroin P.A. Palmiter R.D. Seizures and neuronal damage in mice lacking vesicular zinc Epilepsy Res. 2000 39 153 169 10.1016/S0920-1211(99)00121-7 10759303 · DOI
  42. [45]Adlard P.A. Parncutt J.M. Finkelstein D.I. Bush A.I. Cognitive loss in zinc transporter-3 knock-out mice: A phenocopy for the synaptic and memory deficits of Alzheimer’s disease? J. Neurosci. 2010 30 1631 1636 10.1523/JNEUROSCI.5255-09.2010 20130173 PMC6633978 · DOI
  43. [46]Olesen R.H. Hyde T.M. Kleinman J.E. Smidt K. Rungby J. Larsen A. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain Transl. Psychiatr. 2016 6 e838 10.1038/tp.2016.83 PMC4931611 27300264 · DOI
  44. [47]Beyer N. Coulson D.T. Heggarty S. Ravid R. Irvine G.B. Hellemans J. Johnston J.A. ZnT3 mRNA levels are reduced in Alzheimer’s disease post-mortem brain Mol. Neurodegener. 2009 4 53 10.1186/1750-1326-4-53 20030848 PMC2806356 · DOI
  45. [48]McAllister B.B. Dyck R.H. Zinc transporter 3 (ZnT3) and vesicular zinc in central nervous system function Neurosci. Biobehav. Rev. 2017 80 329 350 10.1016/j.neubiorev.2017.06.006 28624432 · DOI
  46. [49]Huang L. Tepaamorndech S. The SLC30 family of zinc transporters—A review of current understanding of their biological and pathophysiological roles Mol. Asp. Med. 2013 34 548 560 10.1016/j.mam.2012.05.008 23506888 · DOI
  47. [50]Lichten L.A. Cousins R.J. Mammalian zinc transporters: Nutritional and physiologic regulation Annu. Rev. Nutr. 2009 29 153 176 10.1146/annurev-nutr-033009-083312 19400752 · DOI
  48. [51]Jeong J. Eide D.J. The SLC39 family of zinc transporters Mol. Asp. Med. 2013 34 612 619 10.1016/j.mam.2012.05.011 PMC3602797 23506894 · DOI
  49. [52]Wang F. Dufner-Beattie J. Kim B.E. Petris M.J. Andrews G. Eide D.J. Zinc-stimulated endocytosis controls activity of the mouse ZIP1 and ZIP3 zinc uptake transporters J. Biol. Chem. 2004 279 24631 24639 10.1074/jbc.M400680200 15054103 · DOI
  50. [53]Boycott K.M. Beaulieu C.L. Kernohan K.D. Gebril O.H. Mhanni A. Chudley A.E. Redl D. Qin W. Hampson S. Kury S. Autosomal-Recessive Intellectual Disability with Cerebellar Atrophy Syndrome Caused by Mutation of the Manganese and Zinc Transporter Gene SLC39A8 Am. J. Hum. Genet. 2015 97 886 893 10.1016/j.ajhg.2015.11.002 26637978 PMC4678439 · DOI
  51. [54]Baum L. Chan I.H. Cheung S.K. Goggins W.B. Mok V. Lam L. Leung V. Hui E. Ng C. Woo J. Serum zinc is decreased in Alzheimer’s disease and serum arsenic correlates positively with cognitive ability Biometals 2010 23 173 179 10.1007/s10534-009-9277-5 19911117 · DOI
  52. [55]Wang Z.X. Tan L. Wang H.F. Ma J. Liu J. Tan M.S. Sun J.H. Zhu X.C. Jiang T. Yu J.T. Serum Iron, Zinc, and Copper Levels in Patients with Alzheimer’s Disease: A Replication Study and Meta-Analyses J. Alzheimers Dis. 2015 47 565 581 10.3233/JAD-143108 26401693 · DOI
  53. [56]Corona C. Masciopinto F. Silvestri E. Viscovo A.D. Lattanzio R. Sorda R.L. Ciavardelli D. Goglia F. Piantelli M. Canzoniero L.M. Dietary zinc supplementation of 3xTg-AD mice increases BDNF levels and prevents cognitive deficits as well as mitochondrial dysfunction Cell Death Dis. 2010 1 e91 10.1038/cddis.2010.73 21368864 PMC3035902 · DOI
  54. [57]Loef M. von Stillfried N. Walach H. Zinc diet and Alzheimer’s disease: A systematic review Nutr. Neurosci. 2012 15 2 12 10.1179/1476830512Y.0000000010 22583839 · DOI
  55. [58]Maes M. D’Haese P.C. Scharpe S. D’Hondt P. Cosyns P. De Broe M.E. Hypozincemia in depression J. Affect. Disord. 1994 31 135 140 10.1016/0165-0327(94)90117-1 8071476 · DOI
  56. [59]Lai J. Moxey A. Nowak G. Vashum K. Bailey K. McEvoy M. The efficacy of zinc supplementation in depression: Systematic review of randomised controlled trials J. Affect. Disord. 2012 136 e31 e39 10.1016/j.jad.2011.06.022 21798601 · DOI
  57. [60]Yosaee S. Clark C. Keshtkaran Z. Ashourpour M. Keshani P. Soltani S. Zinc in depression: From development to treatment: A comparative/dose response meta-analysis of observational studies and randomized controlled trials Gen. Hosp. Psychiatry 2022 74 110 117 10.1016/j.genhosppsych.2020.08.001 32829928 · DOI
  58. [61]Aoki C. Imai K. Owaki T. Kobayashi-Nakano T. Ushida T. Iitani Y. Nakamura N. Kajiyama H. Kotani T. The Possible Effects of Zinc Supplementation on Postpartum Depression and Anemia Med. Lith. 2022 58 731 10.3390/medicina58060731 PMC9230907 35743994 · DOI
  59. [62]Du K. Liu M.Y. Zhong X. Wei M.J. Decreased circulating Zinc levels in Parkinson’s disease: A meta-analysis study Sci. Rep. 2017 7 3902 10.1038/s41598-017-04252-0 28634347 PMC5478669 · DOI
  60. [63]Sun H. Liu X. Ge H. Wang T. Wang Y. Li W. Association Between Serum Zinc Levels and the Risk of Parkinson’s Disease: A Meta-Analysis Biol. Trace Elem. Res. 2017 179 45 51 10.1007/s12011-017-0941-2 28160244 · DOI
  61. [64]Adani G. Filippini T. Michalke B. Vinceti M. Selenium and Other Trace Elements in the Etiology of Parkinson’s Disease: A Systematic Review and Meta-Analysis of Case-Control Studies Neuroepidemiology 2020 54 1 23 10.1159/000502357 31454800 · DOI
  62. [65]Saini N. Schaffner W. Zinc supplement greatly improves the condition of parkin mutant Drosophila Biol. Chem. 2010 391 513 518 10.1515/bc.2010.052 20302514 · DOI
  63. [66]Bredholt M. Frederiksen J.L. Zinc in Multiple Sclerosis: A Systematic Review and Meta-Analysis Asn Neuro 2016 8 1759091416651511 10.1177/1759091416651511 27282383 PMC4904428 · DOI
  64. [67]Nirooei E. Kashani S. Owrangi S. Malekpour F. Niknam M. Moazzen F. Nowrouzi-Sohrabi P. Farzinmehr S. Akbari H. Blood Trace Element Status in Multiple Sclerosis: A Systematic Review and Meta-analysis Biol. Trace Elem. Res. 2022 200 13 26 10.1007/s12011-021-02621-5 33611740 · DOI
  65. [68]Stoye D. Schubert C. Goihl A. Guttek K. Reinhold A. Brocke S. Grungreiff K. Reinhold D. Zinc aspartate suppresses T cell activation in vitro and relapsing experimental autoimmune encephalomyelitis in SJL/J mice Biometals 2012 25 529 539 10.1007/s10534-012-9532-z 22350510 · DOI
  66. [69]Schubert C. Guttek K. Grungreiff K. Thielitz A. Buhling F. Reinhold A. Brocke S. Reinhold D. Oral zinc aspartate treats experimental autoimmune encephalomyelitis Biometals 2014 27 1249 1262 10.1007/s10534-014-9786-8 25146336 · DOI
  67. [70]Joe P. Petrilli M. Malaspina D. Weissman J. Zinc in schizophrenia: A meta-analysis Gen. Hosp. Psych. 2018 53 19 24 10.1016/j.genhosppsych.2018.04.004 29727763 · DOI
  68. [71]Saghazadeh A. Mahmoudi M. Shahrokhi S. Mojarrad M. Dastmardi M. Mirbeyk M. Rezaei N. Trace elements in schizophrenia: A systematic review and meta-analysis of 39 studies (N = 5151 participants) Nutr. Rev. 2020 78 278 303 10.1093/nutrit/nuz059 31800085 · DOI
  69. [72]Mortazavi M. Farzin D. Zarhghami M. Hosseini S.H. Mansoori P. Nateghi G. Efficacy of Zinc Sulfate as an Add-on Therapy to Risperidone Versus Risperidone Alone in Patients with Schizophrenia: A Double-Blind Randomized Placebo-Controlled Trial Iran. J. Psychiatry Behav. Sci. 2015 9 e853 10.17795/ijpbs-853 26576178 PMC4644625 · DOI
  70. [73]Onaolapo O.J. Ademakinwa O.Q. Olalekan T.O. Onaolapo A.Y. Ketamine-induced behavioural and brain oxidative changes in mice: An assessment of possible beneficial effects of zinc as mono- or adjunct therapy Psychopharmacology 2017 234 2707 2725 10.1007/s00213-017-4666-x 28612134 · DOI
  71. [74]Alizadeh F. Davoodian N. Kazemi H. Ghasemi-Kasman M. Shaerzadeh F. Prenatal zinc supplementation attenuates lipopolysaccharide-induced behavioral impairments in maternal immune activation model Behav. Brain Res. 2020 377 112247 10.1016/j.bbr.2019.112247 31545978 · DOI
  72. [75]Wojciak R.W. Mojs E. Stanislawska-Kubiak M. Samborski W. The serum zinc, copper, iron, and chromium concentrations in epileptic children Epilepsy Res. 2013 104 40 44 10.1016/j.eplepsyres.2012.09.009 23103060 · DOI
  73. [76]Seven M. Basaran S.Y. Cengiz M. Unal S. Yuksel A. Deficiency of selenium and zinc as a causative factor for idiopathic intractable epilepsy Epilepsy Res. 2013 104 35 39 10.1016/j.eplepsyres.2012.09.013 23103062 · DOI
  74. [77]Saghazadeh A. Mahmoudi M. Meysamie A. Gharedaghi M. Zamponi G.W. Rezaei N. Possible role of trace elements in epilepsy and febrile seizures: A meta-analysis Nutr. Rev. 2015 73 760 779 10.1093/nutrit/nuv026 26433016 · DOI
  75. [78]Baraka A.M. Hassab El Nabi W. El Ghotni S. Investigating the role of zinc in a rat model of epilepsy CNS Neurosci. Ther. 2012 18 327 333 10.1111/j.1755-5949.2011.00252.x 22070383 PMC6493370 · DOI
  76. [79]Saad K. El-Houfey A.A. Abd El-Hamed M.A. El-Asheer O.M. Al-Atram A.A. Tawfeek M.S.K. A randomized, double-blind, placebo-controlled clinical trial of the efficacy of treatment with zinc in children with intractable epilepsy Funct. Neurol. 2015 30 181 185 10.11138/FNeur/2015.30.3.181 26415035 PMC4610753 · DOI
  77. [80]Kirazlar M. Erdogan M.A. Erbas O. Anti-seizure effect of zinc on PTZ-induced epilepsy in rat model Bratisl. Lek. Listy 2022 123 648 652 10.4149/BLL_2022_104 36039883 · DOI
  78. [81]McClain C.J. Twyman D.L. Ott L.G. Rapp R.P. Tibbs P.A. Norton J.A. Kasarskis E.J. Dempsey R.J. Young B. Serum and urine zinc response in head-injured patients J. Neurosurg. 1986 64 224 230 10.3171/jns.1986.64.2.0224 3944632 · DOI
  79. [82]Cope E.C. Morris D.R. Scrimgeour A.G. Levenson C.W. Use of zinc as a treatment for traumatic brain injury in the rat: Effects on cognitive and behavioral outcomes Neurorehabilit. Neural Repair 2012 26 907 913 10.1177/1545968311435337 22331212 PMC3888640 · DOI
  80. [83]Young B. Ott L. Kasarskis E. Rapp R. Moles K. Dempsey R.J. Tibbs P.A. Kryscio R. McClain C. Zinc supplementation is associated with improved neurologic recovery rate and visceral protein levels of patients with severe closed head injury J. Neurotrauma 1996 13 25 34 10.1089/neu.1996.13.25 8714860 · DOI
  81. [84]Bertram L. Lill C.M. Tanzi R.E. The genetics of Alzheimer disease: Back to the future Neuron 2010 68 270 281 10.1016/j.neuron.2010.10.013 20955934 · DOI · Paper page
  82. [85]Burnet F.M. A possible role of zinc in the pathology of dementia Lancet 1981 1 186 188 10.1016/S0140-6736(81)90062-3 6162062 · DOI
  83. [87]Grilli M. Goffi F. Memo M. Spano P. Interleukin-1beta and glutamate activate the NF-kappaB/Rel binding site from the regulatory region of the amyloid precursor protein gene in primary neuronal cultures J. Biol. Chem. 1996 271 15002 15007 10.1074/jbc.271.25.15002 8663145 · DOI
  84. [88]Cuesta A. Zambrano A. Royo M. Pascual A. The tumour suppressor p53 regulates the expression of amyloid precursor protein (APP) Biochem. J. 2009 418 643 650 10.1042/BJ20081793 19049493 · DOI
  85. [89]Xie Z. Wu H. Zhao J. Multifunctional roles of zinc in Alzheimer’s disease Neurotoxicology 2020 80 112 123 10.1016/j.neuro.2020.07.003 32717200 · DOI
  86. [90]Dahms S.O. Konnig I. Roeser D. Guhrs K.H. Mayer M.C. Kaden D. Multhaup G. Than M.E. Metal binding dictates conformation and function of the amyloid precursor protein (APP) E2 domain J. Mol. Biol. 2012 416 438 452 10.1016/j.jmb.2011.12.057 22245578 · DOI
  87. [91]Mezzaroba L. Alfieri D.F. Colado S.A. Vissoci R.E. The role of zinc, copper, manganese and iron in neurodegenerative diseases Neurotoxicology 2019 74 230 241 10.1016/j.neuro.2019.07.007 31377220 · DOI · Paper page
  88. [94]Religa D. Strozyk D. Cherny R.A. Volitakis I. Haroutunian V. Winblad B. Naslund J. Bush A.I. Elevated cortical zinc in Alzheimer disease Neurology 2006 67 69 75 10.1212/01.wnl.0000223644.08653.b5 16832080 · DOI
  89. [95]Lee J.Y. Cole T.B. Palmiter R.D. Suh S.W. Koh J.Y. Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice Proc. Natl. Acad. Sci. USA 2002 99 7705 7710 10.1073/pnas.092034699 12032347 PMC124328 · DOI
  90. [96]Sensi S.L. Granzotto A. Siotto M. Squitti R. Copper and Zinc Dysregulation in Alzheimer’s Disease Trends Pharmacol. Sci. 2018 39 1049 1063 10.1016/j.tips.2018.10.001 30352697 · DOI
  91. [97]Sensi S.L. Paoletti P. Bush A.I. Sekler I. Zinc in the physiology and pathology of the CNS Nat. Rev. Neurosci. 2009 10 780 791 10.1038/nrn2734 19826435 · DOI · Paper page
  92. [98]Kawahara M. Mizuno D. Koyama H. Konoha K. Ohkawara S. Sadakane Y. Disruption of zinc homeostasis and the pathogenesis of senile dementia Metallomics 2014 6 209 219 10.1039/C3MT00257H 24247360 · DOI
  93. [99]Arispe N. Diaz J.C. Simakova O. Abeta ion channels. Prospects for treating Alzheimer’s disease with Abeta channel blockers Biochim. Biophys Acta 2007 1768 1952 1965 10.1016/j.bbamem.2007.03.014 17490607 · DOI
  94. [100]Yuan Y. Niu F. Liu Y. Lu N. Zinc and its effects on oxidative stress in Alzheimer’s disease Neurol. Sci. 2014 35 923 928 10.1007/s10072-014-1668-x 24522515 · DOI
  95. [101]Greenough M.A. Camakaris J. Bush A.I. Metal dyshomeostasis and oxidative stress in Alzheimer’s disease Neurochem. Int. 2013 62 540 555 10.1016/j.neuint.2012.08.014 22982299 · DOI
  96. [102]Cuajungco M.P. Goldstein L.E. Nunomura A. Smith M.A. Lim J.T. Atwood C.S. Huang X. Farrag Y.W. Perry G. Bush A.I. Evidence that the beta-amyloid plaques of Alzheimer’s disease represent the redox-silencing and entombment of abeta by zinc J. Biol. Chem. 2000 275 19439 19442 10.1074/jbc.C000165200 10801774 · DOI
  97. [103]Bush A.I. Pettingell W.J. Paradis M.D. Tanzi R.E. Modulation of A beta adhesiveness and secretase site cleavage by zinc J. Biol. Chem. 1994 269 12152 12158 10.1016/S0021-9258(17)32694-7 8163520 · DOI
  98. [104]Tian Z.Y. Wang C.Y. Wang T. Li Y.C. Wang Z.Y. Glial S100A6 Degrades beta-amyloid Aggregation through Targeting Competition with Zinc Ions Aging Dis. 2019 10 756 769 10.14336/AD.2018.0912 31440382 PMC6675528 · DOI
  99. [105]Higashi Y. Segawa S. Matsuo T. Nakamura S. Kikkawa Y. Nishida K. Nagasawa K. Microglial zinc uptake via zinc transporters induces ATP release and the activation of microglia Glia 2011 59 1933 1945 10.1002/glia.21235 22253048 · DOI
  100. [106]Hwang J.J. Park M.H. Choi S.Y. Koh J.Y. Activation of the Trk signaling pathway by extracellular zinc. Role of metalloproteinases J. Biol. Chem. 2005 280 11995 12001 10.1074/jbc.M403172200 15659400 · DOI
  101. [107]Buchman A.S. Yu L. Boyle P.A. Schneider J.A. De Jager P.L. Bennett D.A. Higher brain BDNF gene expression is associated with slower cognitive decline in older adults Neurology 2016 86 735 741 10.1212/WNL.0000000000002387 26819457 PMC4763800 · DOI · Paper page
  102. [108]Peng S. Wuu J. Mufson E.J. Fahnestock M. Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer’s disease J. Neurochem. 2005 93 1412 1421 10.1111/j.1471-4159.2005.03135.x 15935057 · DOI · Paper page
  103. [109]Riffault B. Medina I. Dumon C. Thalman C. Ferrand N. Friedel P. Gaiarsa J.L. Porcher C. Pro-brain-derived neurotrophic factor inhibits GABAergic neurotransmission by activating endocytosis and repression of GABAA receptors J. Neurosci. 2014 34 13516 13534 10.1523/JNEUROSCI.2069-14.2014 25274828 PMC6608319 · DOI
  104. [110]Busche M.A. Konnerth A. Neuronal hyperactivity—A key defect in Alzheimer’s disease? Bioessays 2015 37 624 632 10.1002/bies.201500004 25773221 · DOI · Paper page
  105. [111]Lei P. Ayton S. Bush A.I. The essential elements of Alzheimer’s disease J. Biol. Chem. 2021 296 100105 10.1074/jbc.REV120.008207 33219130 PMC7948403 · DOI
  106. [112]Datki Z. Galik-Olah Z. Janosi-Mozes E. Szegedi V. Kalman J. Hunya A.G. Fulop L. Tamano H. Takeda A. Adlard P.A. Alzheimer risk factors age and female sex induce cortical Abeta aggregation by raising extracellular zinc Mol. Psychiatr. 2020 25 2728 2741 10.1038/s41380-020-0800-y 32518388 · DOI
  107. [113]Smith J.L. Xiong S. Lovell M.A. 4-Hydroxynonenal disrupts zinc export in primary rat cortical cells Neurotoxicology 2006 27 1 5 10.1016/j.neuro.2005.05.009 16125244 · DOI
  108. [115]Moreira G.G. Cristovao J.S. Torres V.M. Carapeto A.P. Rodrigues M.S. Landrieu I. Cordeiro C. Gomes C.M. Zinc Binding to Tau Influences Aggregation Kinetics and Oligomer Distribution Int. J. Mol. Sci. 2019 20 5979 10.3390/ijms20235979 31783644 PMC6928861 · DOI
  109. [116]Huang Y. Wu Z. Cao Y. Lang M. Lu B. Zhou B. Zinc binding directly regulates tau toxicity independent of tau hyperphosphorylation Cell Rep. 2014 8 831 842 10.1016/j.celrep.2014.06.047 25066125 PMC4306234 · DOI
  110. [117]Stoltenberg M. Bush A.I. Bach G. Smidt K. Larsen A. Rungby J. Lund S. Doering P. Danscher G. Amyloid plaques arise from zinc-enriched cortical layers in APP/PS1 transgenic mice and are paradoxically enlarged with dietary zinc deficiency Neuroscience 2007 150 357 369 10.1016/j.neuroscience.2007.09.025 17949919 · DOI
  111. [118]Linkous D.H. Adlard P.A. Wanschura P.B. Conko K.M. Flinn J.M. The effects of enhanced zinc on spatial memory and plaque formation in transgenic mice J. Alzheimers Dis. 2009 18 565 579 10.3233/JAD-2009-1162 19584445 · DOI
  112. [119]Wang C.Y. Wang T. Zheng W. Zhao B.L. Danscher G. Chen Y.H. Wang Z.Y. Zinc overload enhances APP cleavage and Abeta deposition in the Alzheimer mouse brain PLoS ONE 2010 5 e15349 10.1371/journal.pone.0015349 21179415 PMC3003690 · DOI
  113. [120]Craven K.M. Kochen W.R. Hernandez C.M. Flinn J.M. Zinc Exacerbates Tau Pathology in a Tau Mouse Model J. Alzheimers Dis. 2018 64 617 630 10.3233/JAD-180151 29914030 · DOI
  114. [121]Lannfelt L. Blennow K. Zetterberg H. Batsman S. Ames D. Harrison J. Masters C.L. Targum S. Bush A.I. Murdoch R. Safety, efficacy, and biomarker findings of PBT2 in targeting Abeta as a modifying therapy for Alzheimer’s disease: A phase IIa, double-blind, randomised, placebo-controlled trial Lancet Neurol. 2008 7 779 786 10.1016/S1474-4422(08)70167-4 18672400 · DOI · Paper page
  115. [123]Adlard P.A. Cherny R.A. Finkelstein D.I. Gautier E. Robb E. Cortes M. Volitakis I. Liu X. Smith J.P. Perez K. Rapid restoration of cognition in Alzheimer’s transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta Neuron 2008 59 43 55 10.1016/j.neuron.2008.06.018 18614028 · DOI · Paper page
  116. [125]Tassabehji N.M. Corniola R.S. Alshingiti A. Levenson C.W. Zinc deficiency induces depression-like symptoms in adult rats Physiol. Behav. 2008 95 365 369 10.1016/j.physbeh.2008.06.017 18655800 · DOI
  117. [126]Siwek M. Dudek D. Schlegel-Zawadzka M. Morawska A. Piekoszewski W. Opoka W. Zieba A. Pilc A. Popik P. Nowak G. Serum zinc level in depressed patients during zinc supplementation of imipramine treatment J. Affect. Disord. 2010 126 447 452 10.1016/j.jad.2010.04.024 20493532 · DOI
  118. [127]Carroll B.J. Feinberg M. Greden J.F. Tarika J. Albala A.A. Haskett R.F. James N.M. Kronfol Z. Lohr N. Steiner M. A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility Arch. Gen. Psychiatry 1981 38 15 22 10.1001/archpsyc.1981.01780260017001 7458567 · DOI · Paper page
  119. [128]Holsboer F. The dexamethasone suppression test in depressed patients: Clinical and biochemical aspects J. Steroid Biochem. Mol. Biol. 1983 19 251 257 10.1016/S0022-4731(83)80033-8 6887861 · DOI
  120. [129]Arana G.W. Baldessarini R.J. Ornsteen M. The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Commentary and review Arch. Gen. Psychiatry 1985 42 1193 1204 10.1001/archpsyc.1985.01790350067012 3000317 · DOI · Paper page
  121. [130]Takeda A. Tamano H. Kan F. Itoh H. Oku N. Anxiety-like behavior of young rats after 2-week zinc deprivation Behav. Brain Res. 2007 177 1 6 10.1016/j.bbr.2006.11.023 17166602 · DOI
  122. [131]Takeda A. Tamano H. Kan F. Hanajima T. Yamada K. Oku N. Enhancement of social isolation-induced aggressive behavior of young mice by zinc deficiency Life Sci. 2008 82 909 914 10.1016/j.lfs.2008.02.005 18374363 · DOI
  123. [132]Takeda A. Tamano H. Ogawa T. Takada S. Ando M. Oku N. Watanabe M. Significance of serum glucocorticoid and chelatable zinc in depression and cognition in zinc deficiency Behav. Brain Res. 2012 226 259 264 10.1016/j.bbr.2011.09.026 21946308 · DOI
  124. [133]Gregus A. Wintink A.J. Davis A.C. Kalynchuk L.E. Effect of repeated corticosterone injections and restraint stress on anxiety and depression-like behavior in male rats Behav. Brain Res. 2005 156 105 114 10.1016/j.bbr.2004.05.013 15474655 · DOI
  125. [134]Zhao Y. Ma R. Shen J. Su H. Xing D. Du L. A mouse model of depression induced by repeated corticosterone injections Eur. J. Pharmacol. 2008 581 113 120 10.1016/j.ejphar.2007.12.005 18184609 · DOI
  126. [135]Watanabe M. Tamano H. Kikuchi T. Takeda A. Susceptibility to stress in young rats after 2-week zinc deprivation Neurochem. Int. 2010 56 410 416 10.1016/j.neuint.2009.11.014 19931332 · DOI
  127. [136]Mlyniec K. Zinc in the Glutamatergic Theory of Depression Curr. Neuropharmacol. 2015 13 505 513 10.2174/1570159X13666150115220617 26412070 PMC4790399 · DOI
  128. [137]Nowak G. Schlegel-Zawadzka M. Alterations in serum and brain trace element levels after antidepressant treatment: Part I Zinc. Biol. Trace Elem. Res. 1999 67 85 92 10.1007/BF02784278 10065601 · DOI
  129. [138]Doboszewska U. Szewczyk B. Sowa-Kucma M. Mlyniec K. Rafalo A. Ostachowicz B. Lankosz M. Nowak G. Antidepressant activity of fluoxetine in the zinc deficiency model in rats involves the NMDA receptor complex Behav. Brain Res. 2015 287 323 330 10.1016/j.bbr.2015.03.064 25845739 · DOI
  130. [139]Szewczyk B. Poleszak E. Wlaz P. Wrobel A. Blicharska E. Cichy A. Dybala M. Siwek A. Pomierny-Chamiolo L. Piotrowska A. The involvement of serotonergic system in the antidepressant effect of zinc in the forced swim test Prog. Neuro-Psychopharmacol. Biol. Psychiatry 2009 33 323 329 10.1016/j.pnpbp.2008.12.011 19150479 · DOI
  131. [140]Cichy A. Sowa-Kucma M. Legutko B. Pomierny-Chamiolo L. Siwek A. Piotrowska A. Szewczyk B. Poleszak E. Pilc A. Nowak G. Zinc-induced adaptive changes in NMDA/glutamatergic and serotonergic receptors Pharmacol. Rep. 2009 61 1184 1191 10.1016/S1734-1140(09)70182-3 20081255 · DOI
  132. [141]Satala G. Duszynska B. Stachowicz K. Rafalo A. Pochwat B. Luckhart C. Albert P.R. Daigle M. Tanaka K.F. Hen R. Concentration-Dependent Dual Mode of Zn2+ Action at Serotonin 5-HT1A Receptors: In Vitro and In Vivo Studies Mol. Neurobiol. 2016 53 6869 6881 10.1007/s12035-015-9586-3 26660328 PMC5104769 · DOI
  133. [142]Barrondo S. Salles J. Allosteric modulation of 5-HT(1A) receptors by zinc: Binding studies Neuropharmacology 2009 56 455 462 10.1016/j.neuropharm.2008.09.018 18951909 · DOI
  134. [143]Satala G. Duszynska B. Lenda T. Nowak G. Bojarski A.J. Allosteric Inhibition of Serotonin 5-HT7 Receptors by Zinc Ions Mol. Neurobiol. 2018 55 2897 2910 10.1007/s12035-017-0536-0 28455702 PMC5842505 · DOI
  135. [144]Tena-Campos M. Ramon E. Borroto-Escuela D.O. Fuxe K. Garriga P. The zinc binding receptor GPR39 interacts with 5-HT1A and GalR1 to form dynamic heteroreceptor complexes with signaling diversity Biochim. Biophys. Acta 2015 1852 2585 2592 10.1016/j.bbadis.2015.09.003 26365466 · DOI
  136. [145]Tena-Campos M. Ramon E. Lupala C.S. Perez J.J. Koch K.W. Garriga P. Zinc Is Involved in Depression by Modulating G Protein-Coupled Receptor Heterodimerization Mol. Neurobiol. 2016 53 2003 2015 10.1007/s12035-015-9153-y 25855059 · DOI
  137. [146]Borroto-Escuela D.O. Narvaez M. Marcellino D. Parrado C. Narvaez J.A. Tarakanov A.O. Agnati L.F. Diaz-Cabiale Z. Fuxe K. Galanin receptor-1 modulates 5-hydroxtryptamine-1A signaling via heterodimerization Biochem. Biophys. Res. Commun. 2010 393 767 772 10.1016/j.bbrc.2010.02.078 20171159 · DOI
  138. [147]Petrilli M.A. Kranz T.M. Kleinhaus K. Joe P. Getz M. Johnson P. Chao M.V. Malaspina D. The Emerging Role for Zinc in Depression and Psychosis Front. Pharmacol. 2017 8 414 10.3389/fphar.2017.00414 28713269 PMC5492454 · DOI
  139. [148]Szewczyk B. Poleszak E. Sowa-Kucma M. Wrobel A. Slotwinski S. Listos J. Wlaz P. Cichy A. Siwek A. Dybala M. The involvement of NMDA and AMPA receptors in the mechanism of antidepressant-like action of zinc in the forced swim test Amino Acids 2010 39 205 217 10.1007/s00726-009-0412-y 19956994 · DOI
  140. [149]Poleszak E. Szewczyk B. Wlaz A. Fidecka S. Wlaz P. Pilc A. Nowak G. D-serine, a selective glycine/N-methyl-D-aspartate receptor agonist, antagonizes the antidepressant-like effects of magnesium and zinc in mice Pharmacol. Rep. 2008 60 996 1000 19211995
  141. [150]Doboszewska U. Sowa-Kucma M. Mlyniec K. Pochwat B. Holuj M. Ostachowicz B. Pilc A. Nowak G. Szewczyk B. Zinc deficiency in rats is associated with up-regulation of hippocampal NMDA receptor Prog. Neuro-Psychopharmacol. Biol. Psychiatry 2015 56 254 263 10.1016/j.pnpbp.2014.09.013 25290638 · DOI
  142. [151]Belozertseva I.V. Kos T. Popik P. Danysz W. Bespalov A.Y. Antidepressant-like effects of mGluR1 and mGluR5 antagonists in the rat forced swim and the mouse tail suspension tests Eur. Neuropsychopharmacol. 2007 17 172 179 10.1016/j.euroneuro.2006.03.002 16630709 · DOI
  143. [153]Szewczyk B. Poleszak E. Sowa-Kucma M. Siwek M. Dudek D. Ryszewska-Pokrasniewicz B. Radziwon-Zaleska M. Opoka W. Czekaj J. Pilc A. Antidepressant activity of zinc and magnesium in view of the current hypotheses of antidepressant action Pharmacol. Rep. 2008 60 588 589 19066406
  144. [154]Holst B. Egerod K.L. Schild E. Vickers S.P. Cheetham S. Gerlach L.O. Storjohann L. Stidsen C.E. Jones R. Beck-Sickinger A.G. GPR39 signaling is stimulated by zinc ions but not by obestatin Endocrinology 2007 148 13 20 10.1210/en.2006-0933 16959833 · DOI
  145. [155]Mlyniec K. Budziszewska B. Holst B. Ostachowicz B. Nowak G. GPR39 (zinc receptor) knockout mice exhibit depression-like behavior and CREB/BDNF down-regulation in the hippocampus Int. J. Neuropsychopharmacol. 2014 18 pyu002 10.1093/ijnp/pyu002 25609596 PMC4360246 · DOI
  146. [156]Mlyniec K. Doboszewska U. Szewczyk B. Sowa-Kucma M. Misztak P. Piekoszewski W. Trela F. Ostachowicz B. Nowak G. The involvement of the GPR39-Zn(2+)-sensing receptor in the pathophysiology of depression. Studies in rodent models and suicide victims Neuropharmacology 2014 79 290 297 10.1016/j.neuropharm.2013.12.001 24333148 · DOI
  147. [157]Omar N.N. Tash R.F. Fluoxetine coupled with zinc in a chronic mild stress model of depression: Providing a reservoir for optimum zinc signaling and neuronal remodeling Pharmacol. Biochem. Behav. 2017 160 30 38 10.1016/j.pbb.2017.08.003 28801265 · DOI
  148. [158]Saadi R.A. He K. Hartnett K.A. Kandler K. Hershfinkel M. Aizenman E. SNARE-dependent upregulation of potassium chloride co-transporter 2 activity after metabotropic zinc receptor activation in rat cortical neurons in vitro Neuroscience 2012 210 38 46 10.1016/j.neuroscience.2012.03.001 22441041 PMC3358579 · DOI
  149. [159]Siodlak D. Nowak G. Mlyniec K. Interaction between zinc, the GPR39 zinc receptor and the serotonergic system in depression Brain Res. Bull. 2021 170 146 154 10.1016/j.brainresbull.2021.02.003 33549699 · DOI
  150. [160]Perez-Rosello T. Anderson C.T. Schopfer F.J. Zhao Y. Gilad D. Salvatore S.R. Freeman B.A. Hershfinkel M. Aizenman E. Tzounopoulos T. Synaptic Zn2+ inhibits neurotransmitter release by promoting endocannabinoid synthesis J. Neurosci. 2013 33 9259 9272 10.1523/JNEUROSCI.0237-13.2013 23719795 PMC3733213 · DOI
  151. [161]Mlyniec K. Gawel M. Nowak G. Study of antidepressant drugs in GPR39 (zinc receptor(−)/(−)) knockout mice, showing no effect of conventional antidepressants, but effectiveness of NMDA antagonists Behav. Brain Res. 2015 287 135 138 10.1016/j.bbr.2015.03.053 25827929 · DOI
  152. [162]Sen S. Duman R. Sanacora G. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: Meta-analyses and implications Biol. Psychiatry 2008 64 527 532 10.1016/j.biopsych.2008.05.005 18571629 PMC2597158 · DOI · Paper page
  153. [163]Schmidt H.D. Duman R.S. Peripheral BDNF produces antidepressant-like effects in cellular and behavioral models Neuropsychopharmacology 2010 35 2378 2391 10.1038/npp.2010.114 20686454 PMC2955759 · DOI · Paper page
  154. [164]Mlyniec K. Interaction between Zinc, GPR39, BDNF and Neuropeptides in Depression Curr. Neuropharmacol. 2021 19 2012 2019 10.2174/1570159X19666210225153404 33632103 PMC9185795 · DOI
  155. [165]Sowa-Kucma M. Legutko B. Szewczyk B. Novak K. Znojek P. Poleszak E. Papp M. Pilc A. Nowak G. Antidepressant-like activity of zinc: Further behavioral and molecular evidence J. Neural Transm. 2008 115 1621 1628 10.1007/s00702-008-0115-7 18766297 · DOI
  156. [166]Franco J.L. Posser T. Brocardo P.S. Trevisan R. Uliano-Silva M. Gabilan N.H. Santos A.R. Leal R.B. Rodrigues A.L. Farina M. Involvement of glutathione, ERK1/2 phosphorylation and BDNF expression in the antidepressant-like effect of zinc in rats Behav. Brain Res. 2008 188 316 323 10.1016/j.bbr.2007.11.012 18191237 · DOI
  157. [167]Huang Y.Z. Pan E. Xiong Z.Q. McNamara J.O. Zinc-mediated transactivation of TrkB potentiates the hippocampal mossy fiber-CA3 pyramid synapse Neuron 2008 57 546 558 10.1016/j.neuron.2007.11.026 18304484 · DOI
  158. [168]Nagappan G. Woo N.H. Lu B. Ama “zinc” link between TrkB transactivation and synaptic plasticity Neuron 2008 57 477 479 10.1016/j.neuron.2008.02.004 18304477 · DOI
  159. [169]Mlyniec K. Starowicz G. Gawel M. Frackiewicz E. Nowak G. Potential antidepressant-like properties of the TC G-1008, a GPR39 (zinc receptor) agonist J. Affect. Disord. 2016 201 179 184 10.1016/j.jad.2016.05.007 27235821 · DOI
  160. [170]Corniola R.S. Tassabehji N.M. Hare J. Sharma G. Levenson C.W. Zinc deficiency impairs neuronal precursor cell proliferation and induces apoptosis via p53-mediated mechanisms Brain Res. 2008 1237 52 61 10.1016/j.brainres.2008.08.040 18778698 · DOI
  161. [171]Gao H.L. Zheng W. Xin N. Chi Z.H. Wang Z.Y. Chen J. Wang Z.Y. Zinc deficiency reduces neurogenesis accompanied by neuronal apoptosis through caspase-dependent and -independent signaling pathways Neurotox. Res. 2009 16 416 425 10.1007/s12640-009-9072-7 19548052 · DOI
  162. [172]Malberg J.E. Eisch A.J. Nestler E.J. Duman R.S. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus J. Neurosci. 2000 20 9104 9110 10.1523/JNEUROSCI.20-24-09104.2000 11124987 PMC6773038 · DOI · Paper page
  163. [173]Drzyzga L.R. Marcinowska A. Obuchowicz E. Antiapoptotic and neurotrophic effects of antidepressants: A review of clinical and experimental studies Brain Res. Bull. 2009 79 248 257 10.1016/j.brainresbull.2009.03.009 19480984 · DOI
  164. [174]Gower-Winter S.D. Corniola R.S. Morgan T.J. Levenson C.W. Zinc deficiency regulates hippocampal gene expression and impairs neuronal differentiation Nutr. Neurosci. 2013 16 174 182 10.1179/1476830512Y.0000000043 23582512 PMC3757569 · DOI
  165. [176]Rosa A.O. Lin J. Calixto J.B. Santos A.R. Rodrigues A.L. Involvement of NMDA receptors and L-arginine-nitric oxide pathway in the antidepressant-like effects of zinc in mice Behav. Brain Res. 2003 144 87 93 10.1016/S0166-4328(03)00069-X 12946598 · DOI
  166. [177]Brocardo P.S. Assini F. Franco J.L. Pandolfo P. Muller Y.M. Takahashi R.N. Dafre A.L. Rodrigues A.L. Zinc attenuates malathion-induced depressant-like behavior and confers neuroprotection in the rat brain Toxicol. Sci. 2007 97 140 148 10.1093/toxsci/kfm024 17327255 · DOI
  167. [178]Dorri S.A. Hosseinzadeh H. Abnous K. Hasani F.V. Robati R.Y. Razavi B.M. Involvement of brain-derived neurotrophic factor (BDNF) on malathion induced depressive-like behavior in subacute exposure and protective effects of crocin Iran. J. Basic Med. Sci. 2015 18 958 966 26730329 PMC4686579
  168. [179]Bhalla P. Chadha V.D. Dhar R. Dhawan D.K. Neuroprotective effects of zinc on antioxidant defense system in lithium treated rat brain Indian J. Exp. Biol. 2007 45 954 958 18072539
  169. [181]Kelly J.P. Wrynn A.S. Leonard B.E. The olfactory bulbectomized rat as a model of depression: An update Pharmacol. Ther. 1997 74 299 316 10.1016/S0163-7258(97)00004-1 9352586 · DOI
  170. [182]You Z. Luo C. Zhang W. Chen Y. He J. Zhao Q. Zuo R. Wu Y. Pro- and anti-inflammatory cytokines expression in rat’s brain and spleen exposed to chronic mild stress: Involvement in depression Behav. Brain Res. 2011 225 135 141 10.1016/j.bbr.2011.07.006 21767575 · DOI
  171. [183]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. Oxidative stress, inflammation and treatment response in major depression Psychoneuroendocrinology 2017 76 197 205 10.1016/j.psyneuen.2016.11.031 27960139 PMC5272818 · DOI · Paper page
  172. [185]Cousins R.J. Leinart A.S. Tissue-specific regulation of zinc metabolism and metallothionein genes by interleukin 1 Faseb J. 1988 2 2884 2890 10.1096/fasebj.2.13.2458983 2458983 · DOI · Paper page
  173. [186]Kim J.Y. Lee K.J. Kim D.H. Jeong T.C. Lee E.S. Choi Y.M. Jeong H.G. Cytokine-mediated induction of metallothionein in Hepa-1c1c7 cells by oleanolic acid Biochem. Biophys. Res. Commun. 2004 325 792 797 10.1016/j.bbrc.2004.10.121 15541359 · DOI
  174. [187]Liuzzi J.P. Lichten L.A. Rivera S. Blanchard R.K. Aydemir T.B. Knutson M.D. Ganz T. Cousins R.J. Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response Proc. Natl. Acad. Sci. USA 2005 102 6843 6848 10.1073/pnas.0502257102 15863613 PMC1100791 · DOI · Paper page
  175. [188]Maes M. Bosmans E. De Jongh R. Kenis G. Vandoolaeghe E. Neels H. Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression Cytokine 1997 9 853 858 10.1006/cyto.1997.0238 9367546 · DOI · Paper page
  176. [189]Van Hunsel F. Wauters A. Vandoolaeghe E. Neels H. Demedts P. Maes M. Lower total serum protein, albumin, and beta- and gamma-globulin in major and treatment-resistant depression: Effects of antidepressant treatments Psychiatry Res. 1996 65 159 169 10.1016/S0165-1781(96)03010-7 9029664 · DOI
  177. [190]Maes M. De Vos N. Demedts P. Wauters A. Neels H. Lower serum zinc in major depression in relation to changes in serum acute phase proteins J. Affect. Disord. 1999 56 189 194 10.1016/S0165-0327(99)00011-7 10701476 · DOI
  178. [191]Prasad A.S. Meftah S. Abdallah J. Kaplan J. Brewer G.J. Bach J.F. Dardenne M. Serum thymulin in human zinc deficiency J. Clin. Investig. 1988 82 1202 1210 10.1172/JCI113717 3262625 PMC442670 · DOI · Paper page
  179. [192]Maes M. Vandoolaeghe E. Neels H. Demedts P. Wauters A. Meltzer H.Y. Altamura C. Desnyder R. Lower serum zinc in major depression is a sensitive marker of treatment resistance and of the immune/inflammatory response in that illness Biol. Psychiatry. 1997 42 349 358 10.1016/S0006-3223(96)00365-4 9276075 · DOI · Paper page
  180. [193]Prasad A.S. Beck F.W. Grabowski S.M. Kaplan J. Mathog R.H. Zinc deficiency: Changes in cytokine production and T-cell subpopulations in patients with head and neck cancer and in noncancer subjects Proc. Assoc. Am. Phys. 1997 109 68 77 9010918
  181. [196]Kitabayashi C. Fukada T. Kanamoto M. Ohashi W. Hojyo S. Atsumi T. Ueda N. Azuma I. Hirota H. Murakami M. Zinc suppresses Th17 development via inhibition of STAT3 activation Int. Immunol. 2010 22 375 386 10.1093/intimm/dxq017 20215335 · DOI
  182. [197]Robertson M.J. Schacterle R.S. Mackin G.A. Wilson S.N. Bloomingdale K.L. Ritz J. Komaroff A.L. Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and major depression Clin. Exp. Immunol. 2005 141 326 332 10.1111/j.1365-2249.2005.02833.x 15996197 PMC1809442 · DOI
  183. [198]Bjorklund G. Stejskal V. Urbina M.A. Dadar M. Chirumbolo S. Mutter J. Metals and Parkinson’s Disease: Mechanisms and Biochemical Processes Curr. Med. Chem. 2018 25 2198 2214 10.2174/0929867325666171129124616 29189118 · DOI
  184. [199]Kalia L.V. Lang A.E. Parkinson’s disease Lancet 2015 386 896 912 10.1016/S0140-6736(14)61393-3 25904081 · DOI
  185. [200]Brewer G.J. Kanzer S.H. Zimmerman E.A. Molho E.S. Celmins D.F. Heckman S.M. Dick R. Subclinical zinc deficiency in Alzheimer’s disease and Parkinson’s disease Am. J. Alzheimers Dis. Other Dement. 2010 25 572 575 10.1177/1533317510382283 PMC10845304 20841345 · DOI
  186. [201]Zhao H.W. Lin J. Wang X.B. Cheng X. Wang J.Y. Hu B.L. Zhang Y. Zhang X. Zhu J.H. Assessing plasma levels of selenium, copper, iron and zinc in patients of Parkinson’s disease PLoS ONE 2013 8 e83060 10.1371/journal.pone.0083060 24340079 PMC3858355 · DOI
  187. [202]Alimonti A. Ristori G. Giubilei F. Stazi M.A. Pino A. Visconti A. Brescianini S. Sepe M.M. Forte G. Stanzione P. Serum chemical elements and oxidative status in Alzheimer’s disease, Parkinson disease and multiple sclerosis Neurotoxicology 2007 28 450 456 10.1016/j.neuro.2006.12.001 17267042 · DOI
  188. [203]Hegde M.L. Shanmugavelu P. Vengamma B. Rao T.S. Menon R.B. Rao R.V. Rao K.S. Serum trace element levels and the complexity of inter-element relations in patients with Parkinson’s disease J. Trace Elem. Med. Biol. 2004 18 163 171 10.1016/j.jtemb.2004.09.003 15646263 · DOI
  189. [204]Forte G. Bocca B. Senofonte O. Petrucci F. Brusa L. Stanzione P. Zannino S. Violante N. Alimonti A. Sancesario G. Trace and major elements in whole blood, serum, cerebrospinal fluid and urine of patients with Parkinson’s disease J. Neural Transm. 2004 111 1031 1040 10.1007/s00702-004-0124-0 15254791 · DOI
  190. [205]Quiroga M.J. Carroll D.W. Brown T.M. Ascorbate- and zinc-responsive parkinsonism Ann. Pharmacother. 2014 48 1515 1520 10.1177/1060028014545356 25070397 · DOI
  191. [206]Sikora J. Ouagazzal A.M. Synaptic Zinc: An Emerging Player in Parkinson’s Disease Int. J. Mol. Sci. 2021 22 4724 10.3390/ijms22094724 33946908 PMC8125092 · DOI
  192. [207]Gaki G.S. Papavassiliou A.G. Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson’s disease Neuromol. Med. 2014 16 217 230 10.1007/s12017-014-8294-x 24522549 · DOI
  193. [209]Dexter D.T. Carter C.J. Wells F.R. Javoy-Agid F. Agid Y. Lees A. Jenner P. Marsden C.D. Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease J. Neurochem. 1989 52 381 389 10.1111/j.1471-4159.1989.tb09133.x 2911023 · DOI
  194. [210]Good P.F. Hsu A. Werner P. Perl D.P. Olanow C.W. Protein nitration in Parkinson’s disease J. Neuropathol. Exp. Neurol. 1998 57 338 342 10.1097/00005072-199804000-00006 9600227 · DOI · Paper page
  195. [211]Mbiydzenyuy N.E. Ninsiima H.I. Valladares M.B. Pieme C.A. Zinc and linoleic acid pre-treatment attenuates biochemical and histological changes in the midbrain of rats with rotenone-induced Parkinsonism BMC Neurosci. 2018 19 29 10.1186/s12868-018-0429-9 29739324 PMC5941606 · DOI
  196. [212]Park J.S. Koentjoro B. Veivers D. Mackay-Sim A. Sue C.M. Parkinson’s disease-associated human ATP13A2 (PARK9) deficiency causes zinc dyshomeostasis and mitochondrial dysfunction Hum. Mol. Genet. 2014 23 2802 2815 10.1093/hmg/ddt623 24399444 PMC4014187 · DOI
  197. [213]Lee J.Y. Son H.J. Choi J.H. Cho E. Kim J. Chung S.J. Hwang O. Koh J.Y. Cytosolic labile zinc accumulation in degenerating dopaminergic neurons of mouse brain after MPTP treatment Brain Res. 2009 1286 208 214 10.1016/j.brainres.2009.06.046 19559009 · DOI
  198. [214]Tarohda T. Ishida Y. Kawai K. Yamamoto M. Amano R. Regional distributions of manganese, iron, copper, and zinc in the brains of 6-hydroxydopamine-induced parkinsonian rats Anal. Bioanal. Chem. 2005 383 224 234 10.1007/s00216-005-3423-x 16132122 · DOI
  199. [215]Sheline C.T. Zhu J. Zhang W. Shi C. Cai A.L. Mitochondrial inhibitor models of Huntington’s disease and Parkinson’s disease induce zinc accumulation and are attenuated by inhibition of zinc neurotoxicity in vitro or in vivo Neurodegener. Dis. 2013 11 49 58 10.1159/000336558 22627004 · DOI
  200. [216]Xu J. Kao S.Y. Lee F.J. Song W. Jin L.W. Yankner B.A. Dopamine-dependent neurotoxicity of alpha-synuclein: A mechanism for selective neurodegeneration in Parkinson disease Nat. Med. 2002 8 600 606 10.1038/nm0602-600 12042811 · DOI

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Cited by

Sorted by citations

Authors
Wang, B., Fang, T., & Chen, H.
Affiliations
Nanchang University (CN)
Corresponding author
Chen, Hongping
ORCID
Venue
Nutrients
Publisher
MDPI AG
Published
2023-04-29
Volume
15
Issue
9
Pages
2140
ISSN
2072-6643 (ISSN-L)
DOI
10.3390/nu15092140
PMC
PMC10180555
OpenAlex
W4367623803
Cited by
93
References
16
Citations by year
2026: 31 · 2025: 37 · 2024: 20 · 2023: 5
FWCI
3.12
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrients (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Keywords
zinc, zinc homeostasis, central nervous system disorders, synaptic zinc, presynaptic vesicles, neurogenesis, learning and memory, Alzheimer's disease, depression, Parkinson's disease, multiple sclerosis, schizophrenia, epilepsy, traumatic brain injury, trace elements
MeSH terms
Central Nervous System, Central Nervous System Diseases, Humans, Multiple Sclerosis, Trace Elements, Zinc

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