Fluoride Action Network

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Abstract

Although the literature does not provide evidence of health risks from exposure to fluoride (F) in therapeutic doses, questions remain about the effects of long-term and high-dose use on the function of the central nervous system. The objective of this study was to investigate the effect of long-term exposure to F at levels similar to those found in areas of artificial water fluoridation and in areas of endemic fluorosis on biochemical, proteomic, cell density, and functional parameters associated with the cerebellum. For this, mice were exposed to water containing 10 mg F/L or 50 mg F/L (as sodium fluoride) for 60 days. After the exposure period, the animals were submitted to motor tests and the cerebellum was evaluated for fluoride levels, antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (MDA), and nitrite levels (NO). The proteomic profile and morphological integrity were also evaluated. The results showed that the 10 mg F/L dose was able to decrease the ACAP levels, and the animals exposed to 50 mg F/L presented lower levels of ACAP and higher levels of MDA and NO. The cerebellar proteomic profile in both groups was modulated, highlighting proteins related to the antioxidant system, energy production, and cell death, however no neuronal density change in cerebellum was observed. Functionally, the horizontal exploratory activity of both exposed groups was impaired, while only the 50 mg F/L group showed significant changes in postural stability. No motor coordination and balance impairments were observed in both groups. Our results suggest that fluoride may impair the cerebellar oxidative biochemistry, which is associated with the proteomic modulation and, although no morphological impairment was observed, only the highest concentration of fluoride was able to impair some cerebellar motor functions.

*Original abstract online with full text at https://www.mdpi.com/1422-0067/21/19/7297/htm

 

Funding

This study was financed by the National Council for Scientific and Technological Development (CNPq) from Brazilian Ministry of Science, Technology, Innovation and Communications (MCTI) process number: 435093/2018-5 approved by R.L. L.B. and A.D. received CNPq and FAPESP scholarships, respectively. M.B., M.E.C.-L. and C.M. thanks for CNPq fellowship. The APC was funded by Pró-Reitoria de Pesquisa e Pós-graduação da Universidade Federal do Pará (PROPESP-UFPA).

Acknowledgments

We are grateful for the partial financial support from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES—Código Financeiro 001).

References

  1. Zuo, H.; Chen, L.; Kong, M.; Qiu, L.-P.; Lu, P.; Wu, P.; Yang, Y.; Chen, K. Toxic effects of fluoride on organisms. Life Sci. 2018, 198, 18–24. [Google Scholar] [CrossRef]
  2. Barbier, O.; Arreola-Mendoza, L.; Del Razo, L.M. Molecular mechanisms of fluoride toxicity. Chem. Interactions 2010, 188, 319–333. [Google Scholar] [CrossRef] [PubMed]
  3. WHO. Guidelines for Drinking-Water Quality; World Health Organization: Geneva, Switzerland, 2011; Volume 38, pp. 104–108. [Google Scholar]
  4. WHO. Guidelines for Drinking-Water Quality: Fourth Edition Incorporating the First Addendum; World Health Organization: Geneva, Switzerland, 2017. [Google Scholar]
  5. AFTSDR; Service UPH. Toxicological Profile for Fluorides, Hydrogen Fluoride, and Fluorine; Agency for Toxic Substances and Disease Registry: Atlanta, GA, USA, 2003. [Google Scholar]
  6. McDonagh, M.S.; Whiting, P.; Wilson, P.M.; Sutton, A.J.; Chestnutt, I.; Cooper, J.; Misso, K.; Bradley, M.; Treasure, E.; Kleijnen, J. Systematic review of water fluoridation. BMJ 2000, 321, 855–859. [Google Scholar] [CrossRef]
  7. Kobayashi, C.A.N.; Leite, A.L.; Peres-Buzalaf, C.; Carvalho, J.G.; Whitford, G.M.; Everett, E.T.; Siqueira, W.L.; Buzalaf, M.A.R. Bone Response to Fluoride Exposure Is Influenced by Genetics. PLoS ONE 2014, 9, e114343. [Google Scholar] [CrossRef]
  8. Da Silva Pereira, H.A.; de Lima, A.L.; Charone, S.; Lobo, J.G.V.M.; Cestari, T.M.; Peres-Buzalaf, C.; Buzalaf, M.A.R. Proteomic analysis of liver in rats chronically exposed to fluoride. PLoS ONE 2013, 8, e75343. [Google Scholar]
  9. Carvalho, J.G.; Leite, A.L.; Peres-Buzalaf, C.; Salvato, F.; Labate, C.A.; Everett, E.T.; Whitford, G.M.; Buzalaf, M.A.R. Renal Proteome in Mice with Different Susceptibilities to Fluorosis. PLoS ONE 2013, 8, e53261. [Google Scholar] [CrossRef]
  10. Kobayashi, C.A.; Leite, A.L.; Silva, T.L.; Dos Santos, L.D.; Nogueira, F.C.; De Oliveira, R.C.; Palma, M.S.; Domont, G.B.; Buzalaf, M.A. Proteomic analysis of kidney in rats chronically exposed to fluoride. Chem. Interactions 2009, 180, 305–311. [Google Scholar] [CrossRef]
  11. Dionizio, A.S.; Melo, C.G.S.; Sabino-Arias, I.T.; Ventura, T.M.S.; Leite, A.L.; Souza, S.R.G.; Santos, E.X.; Heubel, A.D.; Souza, J.G.; Perles, J.V.C.M.; et al. Chronic treatment with fluoride affects the jejunum: Insights from proteomics and enteric innervation analysis. Sci. Rep. 2018, 8, 1–12. [Google Scholar] [CrossRef]
  12. Melo, C.G.D.S.; Perles, J.V.C.M.; Zanoni, J.N.; De Souza, S.R.G.; Santos, E.X.; Leite, A.L.; Heubel, A.D.; E Souza, C.O.; De Souza, J.G.; Buzalaf, M.A.R. Enteric innervation combined with proteomics for the evaluation of the effects of chronic fluoride exposure on the duodenum of rats. Sci. Rep. 2017, 7, 1070. [Google Scholar] [CrossRef]
  13. Ullah, R.; Zafar, M.S.; Shahani, N. Potential fluoride toxicity from oral medicaments: A review. Iran J. Basic Med. Sci. 2017, 20, 841–848. [Google Scholar]
  14. Bashash, M.; Thomas, D.; Hu, H.; Martinez-Mier, E.A.; Sanchez, B.N.; Basu, N.; Peterson, P.E.; Ettinger, A.S.; Wright, R.; Zhang, Z.; et al. Prenatal fluoride exposure and cognitive outcomes in children at 4 and 6–12 years of age in Mexico. J. Environ. Health Perspect. 2017, 125, 097017. [Google Scholar] [CrossRef]
  15. Choi, A.L.; Sun, G.; Zhang, Y.; Grandjean, P. Developmental Fluoride Neurotoxicity: A Systematic Review and Meta-Analysis. Environ. Health Perspect. 2012, 120, 1362–1368. [Google Scholar] [CrossRef] [PubMed]
  16. Ozsvath, D.L. Fluoride and environmental health: A review. Rev. Environ. Sci. Bio/Technology 2008, 8, 59–79. [Google Scholar] [CrossRef]
  17. Cury, J.; Ricomini-Filho, A.P.; Berti, F.L.P.; Tabchoury, C.P.M. Systemic Effects (Risks) of Water Fluoridation. Braz. Dent. J. 2019, 30, 421–428. [Google Scholar] [CrossRef]
  18. Cheng, X.; Wang, S.; Gao, J. Analysis of MBP, NSE, F-content and CHE activity in brain tissue of rats with chronic fluorosis. J. Chin. J. Endemiol. 2002, 21, 358. [Google Scholar]
  19. Ma, J.; Liu, F.; Liu, P.; Dong, Y.-Y.; Chu, Z.; Hou, T.; Dang, Y. Impact of early developmental fluoride exposure on the peripheral pain sensitivity in mice. Int. J. Dev. Neurosci. 2015, 47, 165–171. [Google Scholar] [CrossRef]
  20. Lee, J.; Han, Y.-E.; Favorov, O.; Tommerdahl, M.; Whitsel, B.; Lee, C.J. Fluoride Induces a Volume Reduction in CA1 Hippocampal Slices Via MAP Kinase Pathway Through Volume Regulated Anion Channels. Exp. Neurobiol. 2016, 25, 72–78. [Google Scholar] [CrossRef] [PubMed]
  21. Agustina, F.; Sofro, Z.M.; Partadiredja, G. Subchronic Administration of High-Dose Sodium Fluoride Causes Deficits in Cerebellar Purkinje Cells But Not Motor Coordination of Rats. Boil. Trace Element Res. 2018, 188, 424–433. [Google Scholar] [CrossRef]
  22. Al-Hayani, A.; Elshal, E.B.; Aal, I.; Al-Shammer, E. Does vitamin E protect against sodium fluoride toxicity on the cerebellar cortex of albino rats. J. Middle East J. Sci. Res. 2013, 16, 1019–1026. [Google Scholar]
  23. Eccles, J.C. Physiology of Motor Control in Man. Ster. Funct. Neurosurg. 1981, 44, 5–15. [Google Scholar] [CrossRef]
  24. Lamont, M.G.; Weber, J.T. The role of calcium in synaptic plasticity and motor learning in the cerebellar cortex. Neurosci. Biobehav. Rev. 2012, 36, 1153–1162. [Google Scholar] [CrossRef]
  25. Valenzuela, C.F.; Lindquist, B.; Zamudio-Bulcock, P.A. A Review of Synaptic Plasticity at Purkinje Neurons with a Focus on Ethanol-Induced Cerebellar Dysfunction. Int. Rev. Neurobiol. 2010, 91, 339–372. [Google Scholar] [CrossRef]
  26. Manto, M.; Mariën, P. Schmahmann’s syndrome – identification of the third cornerstone of clinical ataxiology. Cerebellum Ataxias 2015, 2, 2. [Google Scholar] [CrossRef]
  27. Dunipace, A.; Brizendine, E.; Zhang, W.; Wilson, M.; Miller, L.; Katz, B.; Warrick, J.; Stookey, G. Effect of Aging on Animal Response to Chronic Fluoride Exposure. J. Dent. Res. 1995, 74, 358–368. [Google Scholar] [CrossRef]
  28. Angmar-Mansson, B.; Whitford, G. Enamel Fluorosis Related to Plasma F Levels in the Rat. Caries Res. 1984, 18, 25–32. [Google Scholar] [CrossRef] [PubMed]
  29. Whitford, G.M. The metabolism and toxicity of fluoride. Monogr. Oral Sci. 1996, 16, 1–153. [Google Scholar]
  30. Dec, K.; Lukomska, A.; Maciejewska, D.; Jakubczyk, K.; Baranowska-Bosiacka, I.; Chlubek, D.; Wasik, A.; Gutowska, I. The Influence of Fluorine on the Disturbances of Homeostasis in the Central Nervous System. Boil. Trace Element Res. 2016, 177, 224–234. [Google Scholar] [CrossRef]
  31. Buzalaf, M.A.R.; Whitford, G.M. Fluoride metabolism. In Fluoride and the Oral Environment; Karger Publishers: Basel, Switzerlnad, 2011; pp. 20–36. [Google Scholar]
  32. O’Mullane, D.M.; Baez, R.J.; Jones, S.; A Lennon, M.; Petersen, P.E.; Rugg-Gunn, A.J.; Whelton, H.; Whitford, G.M. Fluoride and Oral Health. Community Dent Heal. 2016, 33, 69–99. [Google Scholar]
  33. Green, R.; Lanphear, B.; Hornung, R.; Flora, D.; Martinez-Mier, E.A.; Neufeld, R.; Ayotte, P.; Muckle, G.; Till, C. Association Between Maternal Fluoride Exposure During Pregnancy and IQ Scores in Offspring in Canada. JAMA Pediatr. 2019, 173, 940. [Google Scholar] [CrossRef]
  34. Karube, H.; Nishitai, G.; Inageda, K.; Kurosu, H.; Matsuoka, M. NaF Activates MAPKs and Induces Apoptosis in Odontoblast-like Cells. J. Dent. Res. 2009, 88, 461–465. [Google Scholar] [CrossRef]
  35. Zhang, M.; Wang, A.; Xia, T.; He, P. Effects of fluoride on DNA damage, S-phase cell-cycle arrest and the expression of NF-?B in primary cultured rat hippocampal neurons. Toxicol. Lett. 2008, 179, 1–5. [Google Scholar] [CrossRef]
  36. Zhang, Y.; Li, W.; Chi, H.S.; Chen, J.; Besten, P.K.D. JNK/c-Jun signaling pathway mediates the fluoride-induced down-regulation of MMP-20 in vitro. Matrix Boil. 2007, 26, 633–641. [Google Scholar] [CrossRef] [PubMed]
  37. Araujo, T.T.; Pereira, H.A.B.S.; Dionizio, A.; Sanchez, C.D.C.; Carvalho, T.D.S.; Fernandes, M.D.S.; Buzalaf, M.A.R. Changes in energy metabolism induced by fluoride: Insights from inside the mitochondria. Chemosphere 2019, 236, 124357. [Google Scholar] [CrossRef] [PubMed]
  38. Iano, F.G.; Ferreira, M.C.; Quaggio, G.B.; Fernandes, M.S.; De Oliveira, R.C.; Ximenes, V.F.; Buzalaf, M.A.R. Effects of chronic fluoride intake on the antioxidant systems of the liver and kidney in rats. J. Fluor. Chem. 2014, 168, 212–217. [Google Scholar] [CrossRef]
  39. Shuhua, X.; Ziyou, L.; Ling, Y.; Fei, W.; Sun, G. A Role of Fluoride on Free Radical Generation and Oxidative Stress in BV-2 Microglia Cells. Mediat. Inflamm. 2012, 2012, 1–8. [Google Scholar] [CrossRef]
  40. Sun, Z.; Zhang, W.; Xue, X.; Zhang, Y.; Niu, R.; Li, X.; Li, B.; Wang, X.; Wang, J. Fluoride decreased the sperm ATP of mice through inhabiting mitochondrial respiration. Chemosphere 2016, 144, 1012–1017. [Google Scholar] [CrossRef]
  41. Waugh, D.T. Fluoride Exposure Induces Inhibition of Sodium-and Potassium-Activated Adenosine Triphosphatase (Na+, K+-ATPase) Enzyme Activity: Molecular Mechanisms and Implications for Public Health. Int. J. Environ. Res. Public Health 2019, 16, 1427. [Google Scholar] [CrossRef]
  42. Izquierdo-Vega, J.A.; Sánchez-Gutiérrez, M.; Del Razo, L.M. Decreased in vitro fertility in male rats exposed to fluoride-induced oxidative stress damage and mitochondrial transmembrane potential loss. Toxicol. Appl. Pharmacol. 2008, 230, 352–357. [Google Scholar] [CrossRef]
  43. Tian, X.-L.; Feng, J.; Dong, N.-S.; Lyu, Y.; Wei, C.-L.; Li, B.; Ma, Y.-Q.; Xie, J.-X.; Qiu, Y.-L.; Song, G.-H.; et al. Subchronic exposure to arsenite and fluoride from gestation to puberty induces oxidative stress and disrupts ultrastructure in the kidneys of rat offspring. Sci. Total. Environ. 2019, 686, 1229–1237. [Google Scholar] [CrossRef]
  44. Dec, K.; Lukomska, A.; Baranowska-Bosiacka, I.; Pilutin, A.; Maciejewska, D.; Skonieczna-?ydecka, K.; Derkacz, R.; Goschorska, M.; Wasik, A.; R?bacz-Maron, E.; et al. Pre-and postnatal exposition to fluorides induce changes in rats liver morphology by impairment of antioxidant defense mechanisms and COX induction. Chemosphere 2018, 211, 112–119. [Google Scholar] [CrossRef]
  45. Dec, K.; Lukomska, A.; Skonieczna-?ydecka, K.; Jakubczyk, K.; Tarnowski, M.; Lubkowska, A.; Baranowska-Bosiacka, I.; Styburski, D.; Skórka-Majewicz, M.; Maciejewska, D.; et al. Chronic Exposure to Fluoride Affects GSH Level and NOX4 Expression in Rat Model of This Element of Neurotoxicity. Biomol. 2020, 10, 422. [Google Scholar] [CrossRef] [PubMed]
  46. Narayanaswamy, M.; Basha, P.M. Effect of Maternal Exposure of Fluoride on Biometals and Oxidative Stress Parameters in Developing CNS of Rat. Biol. Trace Element Res. 2009, 133, 71–82. [Google Scholar] [CrossRef] [PubMed]
  47. Cobb, C.A.; Cole, M.P. Oxidative and nitrative stress in neurodegeneration. Neurobiol. Dis. 2015, 84, 4–21. [Google Scholar] [CrossRef] [PubMed]
  48. Zhu, W.; Zhang, J.; Zhang, Z. Effects of Fluoride on Synaptic Membrane Fluidity and PSD-95 Expression Level in Rat Hippocampus. Biol. Trace Element Res. 2010, 139, 197–203. [Google Scholar] [CrossRef]
  49. Hüttemann, M.; Pecina, P.; Rainbolt, M.; Sanderson, T.H.; Kagan, V.E.; Samavati, L.; Doan, J.W.; Lee, I. The multiple functions of cytochrome c and their regulation in life and death decisions of the mammalian cell: From respiration to apoptosis. Mitochondrion 2011, 11, 369–381. [Google Scholar] [CrossRef]
  50. Ow, Y.-L.P.; Green, D.R.; Hao, Z.; Mak, T.W. Cytochrome c: Functions beyond respiration. Nat. Rev. Mol. Cell Biol. 2008, 9, 532–542. [Google Scholar] [CrossRef]
  51. Neupane, P.; Bhuju, S.; Thapa, N.; Bhattarai, H.K. ATP Synthase: Structure, Function and Inhibition. Biomol. Concepts 2019, 10, 1–10. [Google Scholar] [CrossRef]
  52. Winklhofer, K.F.; Haass, C. Mitochondrial dysfunction in Parkinson’s disease. Biochim. et Biophys. Acta (BBA) – Mol. Basis Dis. 2010, 1802, 29–44. [Google Scholar] [CrossRef]
  53. Boveris, A.; Navarro, A. Brain mitochondrial dysfunction in aging. IUBMB Life 2008, 60, 308–314. [Google Scholar] [CrossRef]
  54. Liu, Y.; Zhang, X. Heat Shock Protein Reports on Proteome Stress. Biotechnol. J. 2018, 13. [Google Scholar] [CrossRef]
  55. Fukai, T.; Ushio-Fukai, M. Superoxide Dismutases: Role in Redox Signaling, Vascular Function, and Diseases. Antioxidants Redox Signal. 2011, 15, 1583–1606. [Google Scholar] [CrossRef] [PubMed]
  56. Park, J.H.; Elpers, C.; Reunert, J.; McCormick, M.L.; Mohr, J.; Biskup, S.; Schwartz, O.; Rust, S.; Grüneberg, M.; Seelhöfer, A.; et al. SOD1 deficiency: A novel syndrome distinct from amyotrophic lateral sclerosis. Brain 2019, 142, 2230–2237. [Google Scholar] [CrossRef] [PubMed]
  57. Fischer, L.R.; Igoudjil, A.; Magrané, J.; Li, Y.; Hansen, J.M.; Manfredi, G.; Glass, J.D. SOD1 targeted to the mitochondrial intermembrane space prevents motor neuropathy in the Sod1 knockout mouse. Brain 2010, 134, 196–209. [Google Scholar] [CrossRef] [PubMed]
  58. Medina, J.F. The multiple roles of Purkinje cells in sensori-motor calibration: To predict, teach and command. Curr. Opin. Neurobiol. 2011, 21, 616–622. [Google Scholar] [CrossRef]
  59. Lamarão-Vieira, K.; Pamplona-Santos, D.; Nascimento, P.C.; Corrêa, M.G.; Bittencourt, L.O.; Dos Santos, S.M.; Cartágenes, S.C.; Fernandes, L.M.P.; Monteiro, M.C.; Maia, C.S.F.; et al. Physical Exercise Attenuates Oxidative Stress and Morphofunctional Cerebellar Damages Induced by the Ethanol Binge Drinking Paradigm from Adolescence to Adulthood in Rats. Oxidative Med. Cell. Longev. 2019, 2019, 1–14. [Google Scholar] [CrossRef]
  60. Valenzuela, C.F.; Jotty, K. Mini-Review: Effects of Ethanol on GABAA Receptor-Mediated Neurotransmission in the Cerebellar Cortex—Recent Advances. Cerebellum 2015, 14, 438–446. [Google Scholar] [CrossRef] [PubMed]
  61. Ito, M.; Yamaguchi, K.; Nagao, S.; Yamazaki, T. Long-Term Depression as a Model of Cerebellar Plasticity. In Progress in Brain Research; Elsevier BV: Amsterdam, The Netherlands, 2014; Volume 210, pp. 1–30. [Google Scholar]
  62. Mapelli, L.; Pagani, M.; Garrido, J.A.; D’Angelo, E.U. Integrated plasticity at inhibitory and excitatory synapses in the cerebellar circuit. Front. Cell. Neurosci. 2015, 9. [Google Scholar] [CrossRef]
  63. D’Angelo, E.U. The Organization of Plasticity in the Cerebellar Cortex: From Synapses to Control. In Progress in Brain Research; Elsevier BV: Amsterdam, The Netherlands, 2014; Volume 210, pp. 31–58. [Google Scholar]
  64. Murphy, M.; Rick, J.; Milgram, N.; Ivy, G. A Simple and Rapid Test of Sensorimotor Function in the Aged Rat. Neurobiol. Learn. Mem. 1995, 64, 181–186. [Google Scholar] [CrossRef]
  65. Fredericks, C.M. Disorders of the cerebellum and its connections. In Pathophysiology of the Motor Systems: Principles and Clinical Presentations; FA Davis: Philadelphia, PA, USA, 1996; pp. 445–466. [Google Scholar]
  66. Miranda, G.H.N.; Gomes, B.A.Q.; Bittencourt, L.O.; Aragão, W.A.B.; Nogueira, L.; Dionizio, A.S.; Buzalaf, M.A.R.; Monteiro, M.C.; Lima, R.R. Chronic Exposure to Sodium Fluoride Triggers Oxidative Biochemistry Misbalance in Mice: Effects on Peripheral Blood Circulation. Oxidative Med. Cell. Longev. 2018, 2018, 1–8. [Google Scholar] [CrossRef]
  67. Brenes, J.C.; Padilla, M.; Fornaguera, J. A detailed analysis of open-field habituation and behavioral and neurochemical antidepressant-like effects in postweaning enriched rats. Behav. Brain Res. 2009, 197, 125–137. [Google Scholar] [CrossRef]
  68. Dixon, L.K.; DeFries, J.C. Development of open-field behavior in mice: Effects of age and experience. Dev. Psychobiol. 1968, 1, 100–107. [Google Scholar] [CrossRef]
  69. Maia, C.D.S.F.; Lucena, G.M.R.D.S.; Corrêa, P.B.F.; Serra, R.B.; Matos, R.W.D.M.; Menezes, F.D.C.; Dos Santos, S.N.; De Sousa, J.B.; Da Costa, E.T.; Ferreira, V.M.M. Interference of ethanol and methylmercury in the developing central nervous system. NeuroToxicology 2009, 30, 23–30. [Google Scholar] [CrossRef]
  70. Oliveira, G.B.; Fontes, E.D.A.; De Carvalho, S.; Da Silva, J.B.; Fernandes, L.M.P.; Oliveira, M.C.S.P.; Prediger, R.D.; Gomes-Leal, W.; Lima, R.R.; Maia, C.S.F. Minocycline mitigates motor impairments and cortical neuronal loss induced by focal ischemia in rats chronically exposed to ethanol during adolescence. Brain Res. 2014, 1561, 23–34. [Google Scholar] [CrossRef]
  71. Fernandes, L.M.P.; Lopes, K.S.; Santana, L.N.S.; Fontes-Júnior, E.A.; Ribeiro, C.H.M.A.; Silva, M.C.F.; Paraense, R.S.D.O.; Crespo-López, M.E.; Gomes, A.R.Q.; Lima, R.R.; et al. Repeated Cycles of Binge-Like Ethanol Intake in Adolescent Female Rats Induce Motor Function Impairment and Oxidative Damage in Motor Cortex and Liver, but Not in Blood. Oxidative Med. Cell. Longev. 2018, 2018, 1–14. [Google Scholar] [CrossRef]
  72. Da Silva, F.B.R.; Cunha, P.A.; Ribera, P.C.; Barros, M.A.; Cartágenes, S.C.; Fernandes, L.M.P.; Teixeira, F.B.; Fontes-Junior, E.A.; Prediger, R.D.; Lima, R.R.; et al. Heavy Chronic Ethanol Exposure From Adolescence to Adulthood Induces Cerebellar Neuronal Loss and Motor Function Damage in Female Rats. Front. Behav. Neurosci. 2018, 12. [Google Scholar] [CrossRef]
  73. Teixeira, F.B.; Santana, L.N.D.S.; Bezerra, F.R.; De Carvalho, S.; Fontes-Júnior, E.A.; Prediger, R.D.; Crespo-López, M.E.; Maia, C.S.F.; Lima, R.R. Chronic Ethanol Exposure during Adolescence in Rats Induces Motor Impairments and Cerebral Cortex Damage Associated with Oxidative Stress. PLoS ONE 2014, 9, e101074. [Google Scholar] [CrossRef]
  74. Ogawa, N.; Hirose, Y.; Ohara, S.; Ono, T.; Watanabe, Y. A simple quantitative bradykinesia test in MPTP-treated mice. Res. Commun. Chem. Pathol. Pharmacol. 1985, 50. [Google Scholar]
  75. Antzoulatos, E.; Jakowec, M.W.; Petzinger, G.M.; Wood, R.I. Sex differences in motor behavior in the MPTP mouse model of Parkinson’s disease. Pharmacol. Biochem. Behav. 2010, 95, 466–472. [Google Scholar] [CrossRef]
  76. Oliveira, A.N.; Pinheiro, A.M.; Belém-Filho, I.J.A.; Fernandes, L.M.P.; Cartágenes, S.C.; Ribera, P.C.; Fontes-Júnior, E.A.; Crespo-López, M.E.; Monteiro, M.C.; Lima, M.O.; et al. Unravelling motor behaviour hallmarks in intoxicated adolescents: Methylmercury subtoxic-dose exposure and binge ethanol intake paradigm in rats. Environ. Sci. Pollut. Res. 2018, 25, 21937–21948. [Google Scholar] [CrossRef]
  77. Fontes-Júnior, E.A.; Maia, C.S.F.; Fernandes, L.M.P.; Gomes-Leal, W.; Costa-Malaquias, A.; Lima, R.R.; Prediger, R.D.; Crespo-López, M.E. Chronic Alcohol Intoxication and Cortical Ischemia: Study of Their Comorbidity and the Protective Effects of Minocycline. Oxidative Med. Cell. Longev. 2016, 2016, 1–10. [Google Scholar] [CrossRef]
  78. Taves, D.R. Separation of fluoride by rapid diffusion using hexamethyldisiloxane. Talanta 1968, 15, 969–974. [Google Scholar] [CrossRef]
  79. Teixeira, F.B.; De Oliveira, A.C.A.; Leão, L.K.D.R.; Fagundes, N.C.F.; Fernandes, R.M.; Fernandes, L.M.P.; Da Silva, M.C.F.; Amado, L.L.; Sagica, F.; De Oliveira, E.H.C.; et al. Exposure to Inorganic Mercury Causes Oxidative Stress, Cell Death, and Functional Deficits in the Motor Cortex. Front. Mol. Neurosci. 2018, 11. [Google Scholar] [CrossRef]
  80. Amado, L.L.; Garcia, M.L.; Ramos, P.; Freitas, R.F.; Zafalon, B.; Ferreira, J.L.R.; Yunes, J.S.; Monserrat, J. A method to measure total antioxidant capacity against peroxyl radicals in aquatic organisms: Application to evaluate microcystins toxicity. Sci. Total. Environ. 2009, 407, 2115–2123. [Google Scholar] [CrossRef]
  81. Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976, 72, 248–254. [Google Scholar] [CrossRef]
  82. Leão, L.K.D.R.; Bittencourt, L.O.; Oliveira, A.C.; Nascimento, P.C.; Miranda, G.H.N.; Ferreira, R.O.; Nabiça, M.; Dantas, K.D.G.F.; Dionizio, A.; Cartágenes, S.; et al. Long-Term Lead Exposure Since Adolescence Causes Proteomic and Morphological Alterations in the Cerebellum Associated with Motor Deficits in Adult Rats. Int. J. Mol. Sci. 2020, 21, 3571. [Google Scholar] [CrossRef]
  83. Corrêa, M.G.; Bittencourt, L.O.; Nascimento, P.C.; Ferreira, R.O.; Aragão, W.A.B.; Silva, M.C.F.; Gomes-Leal, W.; Fernandes, M.S.; Dionizio, A.; Buzalaf, M.R.; et al. Spinal cord neurodegeneration after inorganic mercury long-term exposure in adult rats: Ultrastructural, proteomic and biochemical damages associated with reduced neuronal density. Ecotoxicol. Environ. Saf. 2020, 191, 110159. [Google Scholar] [CrossRef]
  84. Bittencourt, L.O.; Dionizio, A.; Nascimento, P.C.; Puty, B.; Leão, L.K.D.R.; Luz, D.A.; Da Silva, M.C.F.; Amado, L.L.; Leite, A.L.; Buzalaf, M.R.; et al. Proteomic approach underlying the hippocampal neurodegeneration caused by low doses of methylmercury after long-term exposure in adult rats. Met. 2019, 11, 390–403. [Google Scholar] [CrossRef]
  85. Leite, A.L.; Lobo, J.G.V.M.; Pereira, H.A.B.D.S.; Fernandes, M.S.; Martini, T.; Zucki, F.; Sumida, D.H.; Rigalli, A.; Buzalaf, M.A.R. Proteomic Analysis of Gastrocnemius Muscle in Rats with Streptozotocin-Induced Diabetes and Chronically Exposed to Fluoride. PLoS ONE 2014, 9, e106646. [Google Scholar] [CrossRef]
  86. Bindea, G.; Mlecnik, B.; Hackl, H.; Charoentong, P.; Tosolini, M.; Kirilovsky, A.; Fridman, W.H.; Pagès, F.; Trajanoski, Z.; Galon, J. ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 2009, 25, 1091–1093. [Google Scholar] [CrossRef]
  87. Lima, R.R.; Santana, L.N.S.; Fernandes, R.M.; Nascimento, E.M.; Oliveira, A.C.; Fernandes, L.M.P.; Dos Santos, E.M.N.; Tavares, P.A.N.; Dos Santos, I.R.; Gimarães-Santos, A.; et al. Neurodegeneration and Glial Response after Acute Striatal Stroke: Histological Basis for Neuroprotective Studies. Oxidative Med. Cell. Longev. 2016, 2016, 1–15. [Google Scholar] [CrossRef]

*Original abstract online with full text at https://www.mdpi.com/1422-0067/21/19/7297/htm

 

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