Aluminum and Glyphosate Can Synergistically Induce Pineal Gland Pathology: Connection to Gut Dysbiosis and Neurological Disease

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DOI: 10.4236/as.2015.61005    9,091 Downloads   22,587 Views   Citations

ABSTRACT

Many neurological diseases, including autism, depression, dementia, anxiety disorder and Parkinson’s disease, are associated with abnormal sleep patterns, which are directly linked to pineal gland dysfunction. The pineal gland is highly susceptible to environmental toxicants. Two pervasive substances in modern industrialized nations are aluminum and glyphosate, the active ingredient in the herbicide, Roundup?. In this paper, we show how these two toxicants work synergistically to induce neurological damage. Glyphosate disrupts gut bacteria, leading to an overgrowth of Clostridium difficile. Its toxic product, p-cresol, is linked to autism in both human and mouse models. p-Cresol enhances uptake of aluminum via transferrin. Anemia, a result of both aluminum disruption of heme and impaired heme synthesis by glyphosate, leads to hypoxia, which induces increased pineal gland transferrin synthesis. Premature birth is associated with hypoxic stress and with substantial increased risk to the subsequent development of autism, linking hypoxia to autism. Glyphosate chelates aluminum, allowing ingested aluminum to bypass the gut barrier. This leads to anemia-induced hypoxia, promoting neurotoxicity and damaging the pineal gland. Both glyphosate and aluminum disrupt cytochrome P450 enzymes, which are involved in melatonin metabolism. Furthermore, melatonin is derived from tryptophan, whose synthesis in plants and microbes is blocked by glyphosate. We also demonstrate a plausible role for vitamin D3 dysbiosis in impaired gut function and impaired serotonin synthesis. This paper proposes that impaired sulfate supply to the brain mediates the damage induced by the synergistic action of aluminum and glyphosate on the pineal gland and related midbrain nuclei.

Cite this paper

Seneff, S. , Swanson, N. and Li, C. (2015) Aluminum and Glyphosate Can Synergistically Induce Pineal Gland Pathology: Connection to Gut Dysbiosis and Neurological Disease. Agricultural Sciences, 6, 42-70. doi: 10.4236/as.2015.61005.

References

[1] Taira, M., Takase, M. and Sasaki, H. (1998) Sleep Disorder in Children with Autism. Psychiatry and Clinical Neurosciences, 52, 182-183. http://dx.doi.org/10.1111/j.1440-1819.1998.tb01018.x
[2] Bartholemew, K. and Owens, J. (2006) Sleep and ADHD: A Review. Medicine and Health Rhode Island, 89, 91-93.
[3] Corkum, P.H., Tannock, R. and Moldofsy, H. (1998) Sleep Disturbances in Children with Attention Deficit/Hyperactivity Disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 37, 637-646. http://dx.doi.org/10.1097/00004583-199806000-00014
[4] Gruber, R. and Sadeh, A. (2004) Sleep and Neurobehavioral Functioning in Boys with Attention-Deficit/Hyperactivity Disorder and No Reported Breathing Problems. Sleep, 27, 267-273.
[5] Song, C., Lin, A., Bonaccorso, S., Heide, C., Verkerk, R., Kenis, G., et al. (1998) The Inflammatory Response System and the Availability of Plasma Tryptophan in Patients with Primary Sleep Disorders and Major Depression. Journal of Affective Disorders, 49, 211-219.
http://dx.doi.org/10.1016/S0165-0327(98)00025-1
[6] Comella, C.L. (2008) Sleep Disorders in Parkinson’s Disease. Current Treatment Options in Neurology, 10, 215-221. http://dx.doi.org/10.1007/s11940-008-0023-z
[7] Gjerstad, M.D., Wentzel-Larsen, T., Aarsland, D. and Larsen, J.P. (2007) Insomnia in Parkinson’s Disease: Frequency and Progression over Time. Journal of Neurology, Neurosurgery, and Psychiatry, 78, 476-479.
[8] Tandberg, E., Larsen, J.P. and Karlsen, K. (1998) A Community-Based Study of Sleep Disorders in Patients with Parkinson’s Disease. Movement Disorders, 13, 895-899.
http://dx.doi.org/10.1002/mds.870130606
[9] Cohrs, S. (2008) Sleep Disturbances in Patients with Schizophrenia: Impact and Effect of Antipsychotics. CNS Drugs, 22, 939-962. http://dx.doi.org/10.2165/00023210-200822110-00004
[10] Benca, R.M., Obermeyer, W.H., Thisted, R.A. and Gillin, J.C. (1992) Sleep and Psychiatric Disorders: A Meta-Analysis. Archives of General Psychiatry, 49, 651-668.
http://dx.doi.org/10.1001/archpsyc.1992.01820080059010
[11] Tandon, R., Shipley, J.E., Taylor, S., Greden, J.F., Eiser, A., DeQuardo, J. and Goodson, J. (1992) Electroencephalographic Sleep Abnormalities in Schizophrenia: Relationship to Positive/Negative Symptoms and Prior Neuroleptic Treatment. Archives of General Psychiatry, 49, 185-194. http://dx.doi.org/10.1001/archpsyc.1992.01820030017003
[12] Ohayon, M.M. and Roth, T. (2003) Place of Chronic Insomnia in the Course of Depressive and Anxiety Disorders. Journal of Psychiatric Research, 37, 9-15.
http://dx.doi.org/10.1016/S0022-3956(02)00052-3
[13] Coco, D.L., Cannizzaro, E., Spataro, R., Taiellod, A.C. and La Bella, V. (2012) Sleep-Wake Problems in Patients with Amyotrophic Lateral Sclerosis: Implications for Patient Management. Neurodegenerative Disease Management, 2, 315-324. http://dx.doi.org/10.2217/nmt.12.28
[14] Bliwise, D.L. (2004) Sleep Disorders in Alzheimer’s Disease and Other Dementias. Sleep Disorders, 6, 16-28.
[15] Radecki, S.E. and Brunton, S.A. (1993) Management of Insomnia in Office-Based Practice. National Prevalence and Therapeutic Patterns. Archives of Family Medicine, 2, 1129-1134.
http://dx.doi.org/10.1001/archfami.2.11.1129
[16] Li, R.H., Wing, Y.K., Ho, S.C. and Fong, S.Y. (2002) Gender Differences in Insomnia—A Study in the Hong Kong Chinese Population. Journal of Psychosomatic Research, 53, 601-609.
http://dx.doi.org/10.1016/S0022-3999(02)00437-3
[17] CDC (2014) Autism Spectrum Disorder. http://www.cdc.gov/ncbddd/autism/data.html
[18] Dave, D.M. and Fernandez, J.M. (2015) Rising Autism Prevalence: Real or Displacing Other Mental Disorders? Evidence from Demand for Auxiliary Healthcare Workers in California. Economic Inquiry, 53, 448-468. http://dx.doi.org/10.1111/ecin.12137
[19] Nevison, C.D. (2014) A Comparison of Temporal Trends in United States Autism Prevalence to Trends in Suspected Environmental Factors. Environmental Health, 13, 73.
http://dx.doi.org/10.1186/1476-069X-13-73
[20] Macchi, M.M. and Bruce, J.N. (2004) Human Pineal Physiology and Functional Significance of Melatonin. Frontiers in Neuroendocrinology, 25, 177-195.
http://dx.doi.org/10.1016/j.yfrne.2004.08.001
[21] Arendt, J., Middleton, B., Stone, B. and Skene, D. (1999) Complex Effects of Melatonin: Evidence for Photoperiodic Responses in Humans? Sleep, 22, 625-635.
[22] Goldman, H. and Wurtman, R.J. (1964) Flow of Blood to the Pineal Body of the Rat. Nature, 203, 87-88. http://dx.doi.org/10.1038/203087a0
[23] Falnoga, I., Tusek-Znidric, M., Horvat, M. and Stegnar, P. (2000) Mercury, Selenium and Cadmium in Human Autopsy Samples from Idrija Residents and Mercury Mine Workers. Environmental Research, 84, 211-218. http://dx.doi.org/10.1006/enrs.2000.4116
[24] Luke, J. (2001) Fluoride Deposition in the Aged Human Pineal Gland. Caries Research, 35, 125-128.
http://dx.doi.org/10.1159/000047443
[25] Lang, S.B., Marino, A.A., Berkovic, G., Fowler, M. and Abreo, K.D. (1996) Piezoelectricity in the Human Pineal Gland. Bioelectrochemistry and Bioenergetics, 41, 191-195.
http://dx.doi.org/10.1016/S0302-4598(96)05147-1
[26] Shaw, C.A., Kette, S.D., Davidson, R.M. and Seneff, S. (2013) Aluminum’s Role in CNS-Immune System Interactions Leading to Neurological Disorders. Immunome Research, 9, 069.
[27] Strong, M.J. (2001) Chapter 9—Aluminum as an Experimental Neurotoxicant: The Neuropathology and Neurochemistry. In: Exley, C., Ed., Aluminuium and Alzheimer’s Disease: The Science that Describes the Link, Elsevier Science, Amsterdam.
http://dx.doi.org/10.1016/B978-044450811-9/50034-3
[28] Yokel, R.A. and McNamara, P.J. (2001) Aluminium Toxicokinetics: An Updated Minireview. Pharmacology & Toxicology, 88, 159-167.
[29] Alfrey, A.C., LeGendre, G.R. and Kaehny, W.D. (1976) The Dialysis Encephalopathy Syndrome Possible Aluminum Intoxication. The New England Journal of Medicine, 294, 184-188. http://dx.doi.org/10.1056/NEJM197601222940402
[30] Bia, M.J., Cooper, K., Schnall, S., Duffy, T., Hendler, E., Malluche, H. and Solomon, L. (1989) Aluminum Induced Anemia: Pathogenesis and Treatment in Patients on Chronic Hemodialysis. Kidney International, 36, 852-858. http://dx.doi.org/10.1038/ki.1989.271
[31] Dunea, G., Mahurkar, S.D., Mamdani, B. and Smith, E.C. (1978) Role of Aluminum in Dialysis Dementia. Annals of Internal Medicine, 88, 502-504. http://dx.doi.org/10.7326/0003-4819-88-4-502
[32] Sideman, S. and Manor, D. (1982) The Dialysis Dementia Syndrome and Aluminum Intoxication. Nephron, 31, 1-10.
http://dx.doi.org/10.1159/000182595
[33] Heaf, J.G., Pdenphant, J. and Andersen, J.R. (1986) Bone Aluminum Deposition in Maintenance Dialysis Patients Treated with Aluminium-Free Dialysate: Role of Aluminium Hydroxide Consumption. Nephron, 42, 210-216. http://dx.doi.org/10.1159/000183669
[34] Sedman, A.B., Klein, G.L., Merritt, R.J., Miller, N.L., Weber, K.O., Gill, W.L., et al. (1985) Evidence of Aluminum Loading in Infants Receiving Intravenous Therapy. The New England Journal of Medicine, 312, 1337-1343. http://dx.doi.org/10.1056/NEJM198505233122101
[35] Bishop, N.J., Morley, R., Day, J.P. and Lucas, A. (1997) Aluminum Neurotoxicity in Preterm Infants Receiving Intravenous-Feeding Solutions. The New England Journal of Medicine, 336, 1557-1561.
http://dx.doi.org/10.1056/NEJM199705293362203
[36] Sińczuk-Walczak, H., Szymczak, M., Razniewska, G., Matczak, W. and Szymczak, W. (2003) Effects of Occupational Exposure to Aluminum on Nervous System: Clinical and Electroencephalographic Findings. International Journal of Occupational Medicine and Environmental Health, 16, 301-310.
[37] Séralini, G.E., Clair, E., Mesnage, R., Gress, S., Defarge, N., Malatesta, M., et al. (2014) Republished Study: Long-Term Toxicity of a Roundup Herbicide and a Roundup-Tolerant Genetically Modified Maize. Environmental Sciences Europe, 26, 14. http://dx.doi.org/10.1186/s12302-014-0014-5
[38] Mesnage, R., Bernay, B. and Séralini, G.E. (2013) Ethoxylated Adjuvants of Glyphosate-Based Herbicides Are Active Principles of Human Cell Toxicity. Toxicology, 313, 122-128.
http://dx.doi.org/10.1016/j.tox.2012.09.006
[39] Mesnage, R., Defarge, N., de Vendomois, J.S. and Séralini, G.E. (2014) Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles. BioMed Research International, 2014, Article ID: 179691.
[40] USDA (2013) NASS Agricultural Chemical Usage-Field Crops and Potatoes. Agricultural Chemical Usage-Field Crops USDA Economics, Statistics and Market Information System. Albert R. Mann Library, Cornell University.
http://usda.mannlib.cornell.edu/MannUsda/viewDocumentInfo.do?documentID=1560
[41] Swanson, N., Leu, A., Abrahamson, J. and Wallet, B. (2014) Genetically Engineered Crops, Glyphosate and the Deterioration of Health in the United States of America. Journal of Organic Systems, 9, 6-37.
[42] Dennison, C. and Pokras, R. (2000) Design and Operation of the National Hospital Discharge Survey: 1988 Redesign. Vital and Health Statistics. http://www.cdc.gov/nchs/data/series/sr01/sr01039.pdf
[43] CDC (2013) Population Estimates.
http://wonder.cdc.gov/wonder/help/cmf.html#Population%20Inform
[44] CDC (2013) Death Data. Centers for Disease Control and Prevention, National Center for Health Statistics. Compressed Mortality Files on CDC WONDER Online Database. 1999-2010 Data Are Compiled from Compressed Mortality File 1999-2010 Series 20, No. 2P, Released January 2013. 1989-1998 Data Are Compiled from Compressed Mortality File CMF 1989-1998, Series 20, No. 2E, 2003. http://wonder.cdc.gov/mortSQL.html
[45] de Mara, N., Becerril, J.M., Garca-Plazaola, J.I., Hernandez, A., De Felipe, M.R. and Fernandez-Pascual, M. (2006) New Insights on Glyphosate Mode of Action in Nodular Metabolism: Role of Shikimate Accumulation. Journal of Agricultural and Food Chemistry, 54, 2621-2628. http://dx.doi.org/10.1021/jf058166c
[46] Samsel, A. and Seneff, S. (2013) Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases. Entropy, 15, 1416-1463.
http://dx.doi.org/10.3390/e15041416
[47] Fekkes, D., van der Cammen, T.J., van Loon, C.P., Verschoor, C., van Harskamp, F., de Koning, I., et al. (1998) Abnormal Amino Acid Metabolism in Patients with Early Stage Alzheimer Dementia. Journal of Neural Transmission, 105, 287-294. http://dx.doi.org/10.1007/s007020050058
[48] Naushad, S.M., Jain, J.M., Prasad, C.K., Naik, U. and Akella, R.R. (2013) Autistic Children Exhibit Distinct Plasma Amino acid Profile. Indian Journal of Biochemistry and Biophysics, 50, 474-478.
[49] Contardo-Jara, V., Klingelmann, E. and Wiegand, C. (2009) Bioaccumulation of Glyphosate and Its Formulation Roundup Ultra in Lumbriculus variegatus and Its Effects on Biotransformation and Antioxidant Enzymes. Environmental Pollution, 157, 57-63.
http://dx.doi.org/10.1016/j.envpol.2008.07.027
[50] Krüger, M., Schledorn, P., Schrodl, W., Hoppe, H.W., Lutz, W. and Shehata, A.A. (2014) Detection of Glyphosate Residues in Animals and Humans. Journal of Analytical Toxicology, 4, 2.
[51] Krüger, M., Schrodl, W., Pedersen, I. and Shehata, A.A. (2014) Detection of Glyphosate in Malformed Piglets. Journal of Environmental & Analytical Toxicology, 4, 5.
[52] Cryan, J.F. and O’Mahony, S.M. (2011) The Microbiome-Gut-Brain Axis: From Bowel to Behavior. Neurogastroenterology & Motility, 23, 187-192. http://dx.doi.org/10.1111/j.1365-2982.2010.01664.x
[53] Hsiao, E.Y., McBride, S.W., Hsien, S., Sharon, G., Hyde, E.R., McCue, T., et al. (2013) Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders. Cell, 155, 1451-1463. http://dx.doi.org/10.1016/j.cell.2013.11.024
[54] Lafaye, A., Junot, C., Ramounet-Le Gall, B., Fritsch, P., Ezan, E. and Tabet, J.C. (2004) Profiling of Sulfoconjugates in Urine by Using Precursor Ion and Neutral Loss Scans in Tandem Mass Spectrometry. Application to the Investigation of Heavy Metal Toxicity in Rats. Journal of Mass Spectrometry, 39, 655-664. http://dx.doi.org/10.1002/jms.635
[55] Altieri, L., Neri, C., Sacco, R., Curatolo, P., Benvenuto, A., Muratori, F., et al. (2011) Urinary p-Cresol Is Elevated in Small Children with Severe Autism Spectrum disorder. Biomarkers, 16, 252-260.
http://dx.doi.org/10.3109/1354750X.2010.548010
[56] Persico, A.M. and Napolioni, V. (2013) Urinary p-Cresol in Autism Spectrum Disorder. Neurotoxicology and Teratology, 36, 82-90. http://dx.doi.org/10.1016/j.ntt.2012.09.002
[57] Johnson, S., Hollis, C., Kochhar, P., Hennessy, E., Wolke, D. and Marlow, N. (2010) Autism Spectrum Disorders in Extremely Preterm Children. The Journal of Pediatrics, 156, 525-531. http://dx.doi.org/10.1016/j.jpeds.2009.10.041
[58] Limperopoulos, C., Bassan, H., Sullivan, N.R., Soul, J.S., Robertson Jr., R.L., Moore, M., et al. (2008) Positive Screening for Autism in Ex-Preterm Infants: Prevalence and Risk Factors. Pediatrics, 121, 758-765.
http://dx.doi.org/10.1542/peds.2007-2158
[59] Yang, L., Zheng, J., Xu, R., Zhang, Y., Gu, L., Dong, J., et al. (2014) Melatonin Suppresses Hypoxia-Induced Migration of HUVECs via Inhibition of ERK/Rac1 Activation. International Journal of Molecular Sciences, 15, 14102-14121. http://dx.doi.org/10.3390/ijms150814102
[60] Kaur, C., Sivakumar, V., Lu, J. and Ling, E.A. (2007) Increased Vascular Permeability and Nitric Oxide Production in Response to Hypoxia in the Pineal Gland. Journal of Pineal Research, 42, 338-349.
http://dx.doi.org/10.1111/j.1600-079X.2007.00424.x
[61] Clark, S.F. (2008) Iron Deficiency Anemia. Nutrition in Clinical Practice, 23, 128-141.
http://dx.doi.org/10.1177/0884533608314536
[62] Oh, R. and Brown, D.L. (2003) Vitamin B12 Deficiency. American Family Physician, 67, 979-986.
[63] Latif, A., Heinz, P. and Cook, R. (2002) Iron Deficiency in Autism and Asperger Syndrome. Autism, 6, 103-114. http://dx.doi.org/10.1177/1362361302006001008
[64] Krüger, M., Schrodl, W., Neuhaus, J. and Shehata, A.A. (2013) Field Investigations of Glyphosate in Urine of Danish Dairy Cows. Journal of Environmental & Analytical Toxicology, 3.
[65] Pineles, S.L., Avery, R.A. and Liu, G.T. (2010) Vitamin B12 Optic Neuropathy in Autism. Pediatrics, 126, 967-970. http://dx.doi.org/10.1542/peds.2009-2975
[66] Kaiser, L. and Schwartz, K.A. (1985) Aluminum-Induced Anemia. American Journal of Kidney Diseases, 6, 348-352. http://dx.doi.org/10.1016/S0272-6386(85)80092-5
[67] Lee, J.Y., Hwang, K.Y., Nam, I.S., Yim, H.J., Kim, E.N., Jung, J.H., et al. (2001) Clinical Observation of Acute Glyphosate Intoxication. The Korean Journal of Medicine, 60, 383-387. (In Korean)
[68] Ozturk, L., Yazici, A., Eker, S., Gokmen, O., Rmheld, V. and Cakmak, I. (2008) Glyphosate Inhibition of Ferric Reductase Activity in Iron Deficient Sunflower Roots. New Phytologist, 177, 899-906.
http://dx.doi.org/10.1111/j.1469-8137.2007.02340.x
[69] Huynh, Q.K., Kishore, G.M. and Bild, G.S. (1988) 5-Enolpyruvyl Shikimate 3-Phosphate Synthase from Escherichia coli. Journal of Biological Chemistry, 263, 735-739.
[70] Cebeci, O. and Budak, H. (2009) Global Expression Patterns of Three Festuca Species Exposed to Different Doses of Glyphosate Using the Affymetrix GeneChip Wheat Genome Array. Comparative and Functional Genomics, 2009, Article ID: 505701. http://dx.doi.org/10.1155/2009/505701
[71] Cole, D.J. (1985) Mode of Action of Glyphosate—A Literature Analysis. In: Grossbard, E. and Atkinson, D., Eds., The Herbicide Glyphosate, Butterworths, London, 48-74.
[72] Kearney, P.C. and Kaufman, D.D. (1988) Herbicides Chemistry: Degradation and Mode of Action. CRC Press, Boca Raton.
[73] Zaidi, A., Khan, M.S. and Rizvi, P.Q. (2005) Effect of Herbicides on Growth, Nodulation and Nitrogen Content of Greengram. Agronomy for Sustainable Development, 25, 497-504.
http://dx.doi.org/10.1051/agro:2005050
[74] Purgel, M., Takács, Z., Jonsson, C.M., Nagy, L., Andersson, I., Bányai, I., et al. (2009) Glyphosate Complexation to Aluminium(III). An Equilibrium and Structural Study in Solution Using Potentiometry, Multinuclear NMR, ATR-FTIR, ESI-MS and DFT Calculations. Journal of Inorganic Biochemistry, 103, 1426-1438. http://dx.doi.org/10.1016/j.jinorgbio.2009.06.011
[75] Coburn, J.W., Mischel, M.G., Goodman, W.G. and Salusky, I.B. (1991) Calcium Citrate Markedly Enhances Aluminum Absorption from Aluminum Hydroxide. American Journal of Kidney Diseases, 17, 708-711. http://dx.doi.org/10.1016/S0272-6386(12)80356-8
[76] Slanina, P., Frech, W., Ekstrom, L.G., Loof, L., Slorach, S. and Cedergren, A. (1986) Dietary Citric Acid Enhances Absorption of Aluminum in Antacids. Clinical Chemistry, 32, 539-541.
[77] Froment, D.P., Molitoris, B.A., Buddington, B., Miller, N. and Alfrey, A.C. (1989) Site and Mechanism of Enhanced Gastrointestinal Absorption of Aluminum by Citrate. Kidney International, 36, 978-984.
http://dx.doi.org/10.1038/ki.1989.290
[78] Cakmak, I., Yazici, A., Tutus, Y. and Ozturk, L. (2009) Glyphosate Reduced Seed and Leaf Concentrations of Calcium, Manganese, Magnesium, and Iron in Non-Glyphosate Resistant Soybean. European Journal of Agronomy, 31, 114-119.
http://dx.doi.org/10.1016/j.eja.2009.07.001
[79] Carman, J.A., Vlieger, H.R., Ver Steeg, L.J., Sneller, V.E., Robinson, G.W., Clinch-Jones, C.A., et al. (2013) A Long-Term Toxicology Study on Pigs Fed a Combined Genetically Modified (GM) Soy and GM Maize Diet. Journal of Organic Systems, 8, 38-54.
[80] Shehata, A.A, Schrodl, W., Aldin, A.A., Hafez, H.M. and Krüger, M. (2013) The Effect of Glyphosate on Potential Pathogens and Beneficial Members of Poultry Microbiota in Vitro. Current Microbiology, 66, 350-358. http://dx.doi.org/10.1007/s00284-012-0277-2
[81] Abreo, K., Sella, M., Gautreaux, S., De Smet, R., Vogeleere, P., Ringoir, S., et al. (1997) P-Cresol, a Uremic Compound, Enhances the Uptake of Aluminum in Hepatocytes. Journal of the American Society of Nephrology, 8, 935-942.
[82] Kaur, C., Sivakumar, V. and Ling, E.A. (2007) Expression of Tranferrin Receptors in the Pineal Gland of Postnatal and Adult Rats and Its Alteration in Hypoxia and Melatonin Treatment. Glia, 55, 263-273.
[83] de la Monte, S.M., Neely, T.R. and Wands Jr., C.J. (2000) Oxidative Stress and Hypoxia-Like Injury Cause Alzheimer-Type Molecular Abnormalities in Central Nervous System Neurons. Cellular and Molecular Life Sciences CMLS, 57, 1471-1481. http://dx.doi.org/10.1007/PL00000630
[84] Fewtrell, M.S., Bishop, N.J., Edmonds, C.J., Isaacs, E.B. and Lucas, A. (2009) Aluminum Exposure from Parenteral Nutrition in Preterm Infants: Bone Health at 15-Year Follow-Up. Pediatrics, 124, 1372-1379. http://dx.doi.org/10.1542/peds.2009-0783
[85] Jeffery, E.H., Jansen, H.T. and Dellinger, J.A. (1987) In Vivo Interactions of Aluminum with Hepatic Cytochrome P-450 and Metallothionein. Fundamental and Applied Toxicology, 8, 541-548.
http://dx.doi.org/10.1016/0272-0590(87)90139-4
[86] Bidlack, W.R., Brown, R.C., Meskin, M.S., Lee, T.C. and Klein, G.L. (1987) Effect of Aluminum on the Hepatic Mixed Function Oxidase and Drug Metabolism. Nutrient-Drug Interactions, 5, 33-42.
[87] Lamb, D.C., Kelly, D.E., Hanley, S.Z., Mehmood, Z. and Kelly, S.L. (1998) Glyphosate Is an Inhibitor of Plant Cytochrome P450: Functional Expression of Thlaspi arvensae Cytochrome P45071B1/Reductase Fusion Protein in Escherichia coli. Biochemical and Biophysical Research Communications, 244, 110-114. http://dx.doi.org/10.1006/bbrc.1997.7988
[88] Hietanen, E., Linnainmaa, K. and Vainio, H. (1983) Effects of Phenoxyherbicides and Glyphosate on the Hepatic and Intestinal Biotransformation Activities in the Rat. Acta Pharmacologica et Toxicologica, 53, 103-112. http://dx.doi.org/10.1111/j.1600-0773.1983.tb01876.x
[89] Abass, K., Turpeinen, M. and Pelkonen, O. (2009) An Evaluation of the Cytochrome P450 Inhibition Potential of Selected Pesticides in Human Hepatic Microsomes. Journal of Environmental Science and Health, Part B: Pesticides, Food Contaminants, and Agricultural Wastes, 44, 553-563. http://dx.doi.org/10.1080/03601230902997766
[90] Poordad, F.F. (2007) The Burden of Hepatic Encephalopathy. Alimentary Pharmacology & Therapeutics, 25, 3-9. http://dx.doi.org/10.1111/j.1746-6342.2006.03215.x
[91] Ma, X., Idle, J.R., Krausz, K.W. and Gonzalez, F.J. (2005) Metabolism of Melatonin by Human Cytochromes P450. Drug Metabolism and Disposition, 33, 489-494.
http://dx.doi.org/10.1124/dmd.104.002410
[92] Lahiri, D.K., Ge, Y.W., Sharman, E.H. and Bondy, S.C. (2004) Age-Related Changes in Serum Melatonin in Mice: Higher Levels of Combined Melatonin and 6-Hydroxymelatonin Sulfate in the Cerebral Cortex Than Serum, Heart, Liver and Kidney Tissues. Journal of Pineal Research, 36, 217-223. http://dx.doi.org/10.1111/j.1600-079X.2004.00120.x
[93] Adams, J.B., Johansen, L.J., Powell, L.D., Quig, D. and Rubin, R.A. (2011) Gastrointestinal Flora and Gastrointestinal Status in Children with Autism—Comparisons to Typical Children and Correlation with Autism Severity. BMC Gastroenterology, 11. http://dx.doi.org/10.1186/1471-230X-11-22
[94] Gorsky, J.E., Dietz, A.A., Spencer, H. and Os, D. (1979) Metabolic Balance of Aluminum Studied in Six Men. Clinical Chemistry, 25, 1739-1743.
[95] Afzal, N., Murch, S., Thirrupathy, K., Berger, L., Fagbemi, A. and Heuschkel, R. (2003) Constipation with Acquired Megarectum in Children with Autism. Pediatrics, 112, 939-942. http://dx.doi.org/10.1542/peds.112.4.939
[96] Foxx-Orenstein, A.E., Kuemmerle, J.F. and Grider, J.R. (1996) Distinct 5-HT Receptors Mediate the Peristaltic Reflex Induced by Mucosal Stimuli in Human and Guinea Pig Intestine. Gastroenterology, 111, 1281-1290. http://dx.doi.org/10.1053/gast.1996.v111.pm8898642
[97] Kern, J.K., Grannemann, B.D., Trivedi, M.H., Waring, R.H., Ramsden, D.B. and Garver, C.R. (2004) Abnormal Sulfation Chemistry in Autism. In: Ryaskin, O.T., Ed., Trends in Autism Research, Chapter XI, Nova Publishers, Hauppauge.
[98] James, S.J., Cutler, P., Melnyk, S., Jernigan, S., Janak, L., Gaylor, D.W., et al. (2004) Metabolic Biomarkers of Increased Oxidative Stress and Impaired Methylation Capacity in Children with Autism. The American Journal of Clinical Nutrition, 80, 1611-1617.
[99] Lee, B.R., Huseby, S., Koprivova, A., Chételat, A., Wirtz, M., Mugford, S.T., et al. (2012) Effects of fou8/fry1 Mutation on Sulfur Metabolism: Is Decreased Internal Sulfate the Trigger of Sulfate Starvation Response? PLOS ONE, 7, e39425. http://dx.doi.org/10.1371/journal.pone.0039425
[100] Finegold, S.M. (2011) Desulfovibrio Species Are Potentially Important in Regressive Autism. Medical Hypotheses, 77, 270-274. http://dx.doi.org/10.1016/j.mehy.2011.04.032
[101] Tack, G.J., Verbeek, W.H.M., Schreurs, M.W.J. and Mulder, C.J.J. (2010) The Spectrum of Celiac Disease: Epidemiology, Clinical Aspects and Treatment. Nature Reviews Gastroenterology and Hepatology, 7, 204-213.
http://dx.doi.org/10.1038/nrgastro.2010.23
[102] Samsel, A. and Seneff, S. (2013) Glyphosate, Pathways to Modern Diseases II: Celiac Sprue and Gluten Intolerance. Interdisciplinary Toxicology, 6, 159-184. http://dx.doi.org/10.2478/intox-2013-0026
[103] Smith, A. and Macfarlane, G.T. (1997) Formation of Phenolic and Indolic Compounds by Anaerobic Bacteria in the Human Large Intestine. Microbial Ecology, 33, 180-188.
http://dx.doi.org/10.1007/s002489900020
[104] Mathus, T.L., Townsend, D.E. and Miller, K.W. (1995) Anaerobic Biogenesis of Phenol and p-Cresol from L-Tyrosine. Fuel, 74, 1505-1508. http://dx.doi.org/10.1016/0016-2361(95)00109-I
[105] Holick, M.F. (2005) The Vitamin D Epidemic and Its Health Consequences. Journal of Nutrition, 135, 2739-2748.
[106] Grant, W.B. and Soles, C.M. (2009) Epidemiologic Evidence Supporting the Role of Maternal Vitamin D Deficiency as a Risk Factor for the Development of Infantile Autism. Dermato-Endocrinology, 1, 223-228. http://dx.doi.org/10.4161/derm.1.4.9500
[107] Wikvall, K. (2001) Cytochrome P450 Enzymes in the Bioactivation of Vitamin D to Its Hormonal Form. International Journal of Molecular Medicine, 7, 201-209.
[108] Bolt, M.J.G., Liu, W., Qiao, G., Kong, J., Zheng, W., Krausz, T., et al. (2004) Critical Role of Vitamin D in Sulfate Homeostasis: Regulation of the Sodium-Sulfate Cotransporter by 1,25-Dihydroxyvitamin D3. American Journal of Physiology—Endocrinology and Metabolism, 287, E744-E749. http://dx.doi.org/10.1152/ajpendo.00151.2004
[109] Fernandes, I., Hampson, G., Cahours, X., Morin, P., Coureau, C., Couette, S., et al. (1997) Abnormal Sulfate Metabolism in Vitamin D-Deficient Rats. Journal of Clinical Investigation, 100, 2196-2203.
http://dx.doi.org/10.1172/JCI119756
[110] Murch, S.H., MacDonald, T.T., Walker-Smith, J.A., Lionetti, P., Levin, M. and Klein, N.J. (1993) Disruption of Sulphated Glycosaminoglycans in Intestinal Inflammation. The Lancet, 341, 711-714.
http://dx.doi.org/10.1016/0140-6736(93)90485-Y
[111] Liu, W., Chen, Y., Golan, M.A., Annunziata, M.L., Du, J., Dougherty, U., et al. (2013) Intestinal Epithelial Vitamin D Receptor Signaling Inhibits Experimental Colitis. Journal of Clinical Investigation, 123, 3983-3996. http://dx.doi.org/10.1172/JCI65842
[112] Yuk, J.M., Shin, D.M., Lee, H.M., Yang, C.S., Jin, H.S., Kim, K.K., et al. (2009) Vitamin D3 Induces Autophagy in Human Monocytes/Macrophages via Cathelicidin. Cell Host and Microbe, 6, 231-243.
http://dx.doi.org/10.1016/j.chom.2009.08.004
[113] Colston, K.W., Mackay, A.G., Finlayson, C., Wu, J.C. and Maxwell, J.C. (1994) Localisation of Vitamin D Receptor in Normal Human Duodenum and in Patients with Coeliac Disease. Gut, 35, 1219-1225.
http://dx.doi.org/10.1136/gut.35.9.1219
[114] Costedio, M.M., Hyman, N. and Mawe, G.M. (2007) Serotonin and Its Role in Colonic Function and in Gastrointestinal Disorders. Diseases of the Colon & Rectum, 50, 376-388. http://dx.doi.org/10.1007/s10350-006-0763-3
[115] Wade, P.R., Chen, J., Jaffe, B., Kassem, I.S., Blakely, R.D. and Gershon, M.D. (1996) Localization and Function of a 5-HT Transporter in Crypt Epithelia of the Gastrointestinal Tract. The Journal of Neuroscience, 16, 2352-2364.
[116] Hagbom, M., Istrate, C., Engblom, D., Karlsson, T., Rodriguez-Diaz, J., Buesa, J., et al. (2011) Rotavirus Stimulates Release of Serotonin (5-HT) from Human Enterochromaffin Cells and Activates Brain Structures Involved in Nausea and Vomiting. PLOS Pathogens, 7, e1002115. http://dx.doi.org/10.1371/journal.ppat.1002115
[117] Lundgren, O. and Svensson, L. (2001) Pathogenesis of Rotavirus diarrhea. Microbes and Infection, 3, 1145-1156. http://dx.doi.org/10.1016/S1286-4579(01)01475-7
[118] Suominen, T., Uutela, P., Ketola, R.A., Bergquist, J., Hillered, L., Finel, M., et al. (2013) Determination of Serotonin and Dopamine Metabolites in Human Brain Microdialysis and Cerebrospinal Fluid Samples by UPLC-MS/MS: Discovery of Intact Glucuronide and Sulfate Conjugates. PLOS ONE, 8, e68007. http://dx.doi.org/10.1371/journal.pone.0068007
[119] Nau Jr., F., Yu, B., Martin, D. and Nichols, C.D. (2013) Serotonin 5-HT2A Receptor Activation Blocks TNF-α Mediated Inflammation in Vivo. PLOS ONE, 8, e75426.
http://dx.doi.org/10.1371/journal.pone.0075426
[120] Westphal, V., Murch, S., Kim, S., Srikrishna, G., Winchester, B., Day, R. and Freeze, H.H. (2000) Reduced Heparan Sulfate Accumulation in Enterocytes Contributes to Protein-Losing Enteropathy in a Congenital Disorder of Glycosylation. American Journal of Pathology, 157, 1917-1925. http://dx.doi.org/10.1016/S0002-9440(10)64830-4
[121] Day, R., Ilyas, M., Daszak, P., Talbot, I. and Forbes, A. (1999) Expression of Syndecan-1 in Inflammatory Bowel Disease and a Possible Mechanism of Heparin Therapy. Digestive Diseases and Sciences, 44, 2508-2515. http://dx.doi.org/10.1023/A:1026647308089
[122] Tanabe, H., Yokota, K. and Kohgo, Y. (1999) Localization of Syndecan-1 in Human Gastric Mucosa Associated with Ulceration. The Journal of Pathology, 187, 338-344.
[123] Murch, S.H., Phillips, D., Walker-Smith, J.A., Winyard, P.J.D., Meadows, N., Koletzko, S., et al. (1997) Congenital Enterocyte Heparan Sulphate Deficiency with Massive Albumin Loss, Secretory Diarrhoea, and Malnutrition. The Lancet, 347, 1299-1301. http://dx.doi.org/10.1016/S0140-6736(96)90941-1
[124] Ciccocioppo, R., Di Sabatino, A., Parroni, R., Muzi, P., D’Alò, S., Ventura, T., et al. (2001) Increased Enterocyte Apoptosis and Fas-Fas Ligand System in Celiac Disease. American Journal of Clinical Pathology, 115, 494-503. http://dx.doi.org/10.1309/UV54-BHP3-A66B-0QUD
[125] Adriaanse, M.P., Tack, G.J., Passos, V.L., Damoiseaux, J.G., Schreurs, M.W., van Wijck, K., et al. (2013) Serum I-FABP as Marker for Enterocyte Damage in Coeliac Disease and Its Relation to Villous Atrophy and Circulating Autoantibodies. Alimentary Pharmacology & Therapeutics, 37, 482-490. http://dx.doi.org/10.1111/apt.12194
[126] Bracken, S., Byrne, G., Kelly, J., Jackson, J. and Feighery, C. (2008) Altered Gene Expression in Highly Purified Enterocytes from Patients with Active Coeliac Disease. BMC Genomics, 9.
http://dx.doi.org/10.1186/1471-2164-9-377
[127] Higaki, M., Takahashi, M., Suzuki, T. and Sahashi, Y. (1965) Biological Activities in Animals of Vitamin D III. Biogenesis of Vitamin D Sulfate in Animal Tissues. The Journal of Vitaminology, 11, 261-265.
http://dx.doi.org/10.5925/jnsv1954.11.261
[128] Higaki, M., Takahashi, M., Suzuki, T. and Sahash, Y. (1965) Metabolic Activities of Vitamin D in Animals. IV. Distribution of Vitamin D Sulfokinase in Animal Tissues and Its Isolation. The Journal of Vitaminology, 11, 266-270. http://dx.doi.org/10.5925/jnsv1954.11.266
[129] Han, X.M., Holtzman, D., McKeel Jr., D.W., Kelley, J. and Morris, J.C. (2002) Substantial Sulfatide Deficiency and Ceramide Elevation in Very Early Alzheimer’s Disease: Potential Role in Disease Pathogenesis. Journal of Neurochemistry, 82, 809-818.
http://dx.doi.org/10.1046/j.1471-4159.2002.00997.x
[130] Irie, F., Badie-Mahdavi, H. and Yamaguchi, Y. (2012) Autism-Like Socio-Communicative Deficits and Stereotypies in Mice Lacking Heparan Sulfate. Proceedings of the National Academy of Sciences of the United States of America, 109, 5052-5056. http://dx.doi.org/10.1073/pnas.1117881109
[131] Pearson, B.L., Corley, M.J., Vasconcellos, A., Blanchard, D.C. and Blanchard, R.J. (2013) Heparan Sulfate Deficiency in Autistic Postmortem Brain Tissue from the Subventricular Zone of the Lateral Ventricles. Behavioural Brain Research, 243, 138-145. http://dx.doi.org/10.1016/j.bbr.2012.12.062
[132] Bishop, J.R., Schuksz, M. and Esko, J.D. (2007) Heparan Sulphate Proteoglycans Fine-Tune Mammalian Physiology. Nature, 446, 1030-1037. http://dx.doi.org/10.1038/nature05817
[133] Bennett-Clarke, C.A., Leslie, M.J., Lane, R.D. and Rhoades, R.W. (1994) Effect of Serotonin Depletion on Vibrissa-Related Patterns of Thalamic Afferents in the Rats Somatosensory Cortex. The Journal of Neuroscience, 14, 7594-7607.
[134] Mazer, C., Muneyyirci, J., Taheny, K., Raio, N., Borella, A. and Whitaker-Azmitia, P. (1997) Serotonin Depletion during Synaptogenesis Leads to Decreased Synaptic Density and Learning Deficits in the Adult Rat: A Possible Model of Neurodevelopmental Disorders with Cognitive Deficits. Brain Research, 760, 68-73. http://dx.doi.org/10.1016/S0006-8993(97)00297-7
[135] Casanova, M.F., Buxhoeveden, D.P., Switala, A.E. and Roy, E. (2002) Minicolumnar Pathology in Autism. Neurology, 58, 428-432. http://dx.doi.org/10.1212/WNL.58.3.428
[136] Boylan, C.B., Blue, M.E. and Hohmann, C.F. (2007) Modeling Early Cortical Serotonergic Deficits in Autism. Behavioural Brain Research, 176, 94-108. http://dx.doi.org/10.1016/j.bbr.2006.08.026
[137] Hohmann, C.F., Walker, E.M., Boylan, C.B. and Blue, M.E. (2007) Neonatal Serotonin Depletion Alters Behavioral Responses to Spatial Change and Novelty. Brain Research, 1139, 163-177.
http://dx.doi.org/10.1016/j.brainres.2006.12.095
[138] Kocovská, E., Fernell, E., Billstedt, E., Minnis, H. and Gillberg, C. (2012) Vitamin D and Autism: Clinical Review. Research in Developmental Disabilities, 33, 1541-1550.
http://dx.doi.org/10.1016/j.ridd.2012.02.015
[139] Patrick, R.P. and Ames, B.N. (2014) Vitamin D Hormone Regulates Serotonin Synthesis. Part 1: Relevance for Autism. FASEB Journal, 28, 2398-2413. (ePub Ahead of Print) http://dx.doi.org/10.1096/fj.13-246546
[140] Kuberan, B., Lech, M., Borjigin, J. and Rosenberg, R.D. (2004) Light-Induced 3-O-Sulfotransferase Expression Alters Pineal Heparan Sulfate Fine Structure. A Surprising Link to Circadian Rhythm. Journal of Biological Chemistry, 279, 5053-5054. http://dx.doi.org/10.1074/jbc.C300492200
[141] Tyce, G.M., Messick, J.M., Yaksh, T.L., Byer, D.E., Danielson, D.R. and Rorie, D.K. (1986) Amine Sulfate Formation in the Central Nervous System. Federation proceedings, 45, 2247-2253.
[142] Kurth, F., Narr, K.L., Woods, R.P., O’Neill, J., Alger, J.R., Caplan, R., et al. (2011) Diminished Gray Matter within the Hypothalamus in Autism Disorder: A Potential Link to Hormonal Effects? Biological Psychiatry, 70, 278-282. http://dx.doi.org/10.1016/j.biopsych.2011.03.026
[143] Weaver, D.R., Rivkees, S.A. and Reppert, S.M. (1989) Localization and Characterization of Melatonin Receptors in Rodent Brain by in Vitro Autoradiography. The Journal of Neuroscience, 9, 2581-2590.
[144] Rosenwasser, A.M., Trubowitsch, G. and Adler, N.T. (1985) Circadian Rhythm in Metabolic Activity of Suprachiasmatic, Supraoptic and Raphe Nuclei. Neuroscience Letters, 58, 183-187.
http://dx.doi.org/10.1016/0304-3940(85)90161-2
[145] Seneff, S., Lauritzen, A., Davidson, R. and Lentz-Marino, L. (2012) Is Endothelial Nitric Oxide Synthase a Moon-lighting Protein Whose Day Job Is Cholesterol Sulfate Synthesis? Implications for Cholesterol Transport, Diabetes and Cardiovascular Disease. Entropy, 14, 2492-2530. http://dx.doi.org/10.3390/e14122492
[146] Baulieu, E.E. and Robel, P. (1998) Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulfate (DHEAS) as Neuroactive Neurosteroids. Proceedings of the National Academy of Sciences of the United States of America, 95, 4089-4091. http://dx.doi.org/10.1073/pnas.95.8.4089
[147] Vallée, M., Mayo, W. and Le Moal, M. (2001) Role of Pregnenolone, Dehydroepiandrosterone and Their Sulfate Esters on Learning and Memory in Cognitive Aging. Brain Research Reviews, 37, 301-312. http://dx.doi.org/10.1016/S0165-0173(01)00135-7
[148] Beaujean, D., Mensah-Nyagan, A.G., Van Luu-The, J.L.D., Pelletier, G. and Vaudry, H. (1999) Immunocytochemical Localization and Biological Activity of Hydroxysteroid Sulfotransferase in the Frog Brain. Journal of Neurochemistry, 72, 848-857.
http://dx.doi.org/10.1046/j.1471-4159.1999.720848.x
[149] Robel, P. and Baulieu, E.E. (1994) Neurosteroids: Biosynthesis and Function. Trends in Endocrinology and Metabolism, 5, 1-8. http://dx.doi.org/10.1016/1043-2760(94)90114-7
[150] Murialdo, G., Nobili, F., Rollero, A., Gianelli, M.V., Copello, F., Rodriguez, G., et al. (2000) Hippocampal Perfusion and Pituitary-Adrenal Axis in Alzheimer’s Disease. Neuropsychobiology, 42, 51-57.
http://dx.doi.org/10.1159/000026672
[151] San Martin, M. and Touitou, Y. (2000) DHEA-Sulfate Causes a Phase-Dependent Increase in Melatonin Secretion: A Study of Perifused Rat Pineal Glands. Steroids, 65, 491-496. http://dx.doi.org/10.1016/S0039-128X(00)00111-2
[152] Schafield, M., Jenski, L.J., Dumaual, A.C. and Stillwell, W. (1998) Cholesterol versus Cholesterol Sulfate: Effects on Properties of Phospholipid Bilayers Containing Docosahexaenoic Acid. Chemistry and Physics of Lipids, 95, 23-36.
http://dx.doi.org/10.1016/S0009-3084(98)00065-6
[153] Sawazaki, S., Salem Jr., N. and Kim, H.Y. (1994) Lipoxygenation of Docosahexaenoic Acid by the Rat Pineal Body. Journal of Neurochemistry, 62, 2437-2447.
http://dx.doi.org/10.1046/j.1471-4159.1994.62062437.x
[154] Zaouali-Ajina, M., Gharib, A., Durand, G., Gazzah, N., Claustrat, B., Gharib, C., et al. (1999) Dietary Docosahexaenoic Acid-Enriched Phospholipids Normalize Urinary Melatonin Excretion in Adult (n-3) Polyunsaturated Fatty Acid-Deficient Rats. Journal of Nutrition, 129, 2074-2080.
[155] Jiang, Y.J., Kim, P., Elias, P.M. and Feingold, K.R. (2005) LXR and PPAR Activators Stimulate Cholesterol Sulfotransferase Type 2 Isoform 1b in Human Keratinocytes. Journal of Lipid Research, 46, 2657-2666. http://dx.doi.org/10.1194/jlr.M500235-JLR200
[156] Wang, L., Schuster, G.U., Hultenby, K., Zhang, Q., Andersson, S. and Gustafsson, J.A. (2002) Liver X Receptors in the Central Nervous System: From Lipid Homeostasis to Neuronal Degeneration. Proceedings of the National Academy of Sciences of the United States of America, 99, 13878-13883. http://dx.doi.org/10.1073/pnas.172510899
[157] Bai, Q., Xu, L., Kakiyama, G., Runge-Morris, M.A., Hylemon, P.B., Yin, L., et al. (2011) Sulfation of 25-Hydroxy-cholesterol by SULT2B1b Decreases Cellular Lipids via the LXR/SREBP-1c Signaling Pathway in Human Aortic Endothelial Cells. Atherosclerosis, 214, 350-356.
http://dx.doi.org/10.1016/j.atherosclerosis.2010.11.021
[158] Erlinger, T.P., Miller III., E.R., Charleston, J. and Appel, L.J. (2003) Inflammation Modifies the Effects of a Reduced-Fat Low-Cholesterol Diet on Lipids: Results from the DASH-Sodium Trial. Circulation, 108, 150-154. http://dx.doi.org/10.1161/01.CIR.0000080288.30567.86
[159] Heliovaara, M.K., Teppo, A.M., Karonen, S.L. and Ebeling, P. (2006) Inflammation Affects Lipid Metabolism during Recovery from Hyperinsulinaemia. European Journal of Clinical Investigation, 36, 860-865. http://dx.doi.org/10.1111/j.1365-2362.2006.01730.x
[160] Xie, L., Kang, H., Xu, Q., Chen, M.J., Liao, Y., Thiyagarajan, M., et al. (2013) Sleep Drives Metabolite Clearance from the Adult Brain. Science, 342, 373-377. http://dx.doi.org/10.1126/science.1241224
[161] Nixon, R.A. (2005) Endosome Function and Dysfunction in Alzheimer’s Disease and Other Neurodegenerative Diseases. Neurobiology of Aging, 26, 373-382.
http://dx.doi.org/10.1016/j.neurobiolaging.2004.09.018
[162] Nixon, R.A., Wegiel, J., Kumar, A., Yu, W.H., Peterhoff, C., Cataldo, A., et al. (2005) Extensive Involvement of Autophagy in Alzheimer’s Disease: An Immunoelectron Microscopy Study. Journal of Neuropathology & Experimental, 64, 113-122.
[163] Sokolowski, J.D. and Mandell, J.W. (2011) Phagocytic Clearance in Neurodegeneration. American Journal of Pathology, 178, 1416-1428. http://dx.doi.org/10.1016/j.ajpath.2010.12.051
[164] Wiegmann, E.M., Westendorf, E., Kalus, I., Pringle, T.H., Lübke, T. and Dierks, T. (2013) Arylsulfatase K, a Novel Lysosomal Sulfatase. Journal of Biological Chemistry, 288, 30019-30028. http://dx.doi.org/10.1074/jbc.M113.499541
[165] Kurz, T., Eaton, J.W. and Brunk, U.T. (2011) The Role of Lysosomes in Iron Metabolism and Recycling. The International Journal of Biochemistry & Cell Biology, 43, 1686-1697.
http://dx.doi.org/10.1016/j.biocel.2011.08.016
[166] Kehrer, J.P. (2000) The Haber-Weiss Reaction and Mechanisms of Toxicity. Toxicology, 149, 43-50.
http://dx.doi.org/10.1016/S0300-483X(00)00231-6
[167] Ross, M.A., Long, W.F. and Williamson, F.B. (1992) Inhibition by Heparin of Fe(II)-Catalysed Free-Radical Peroxidation of Linolenic Acid. Biochemical Journal, 286, 717-720.
[168] Egeberg, M., Kjeken, R., Kolset, S.O., Berg, T. and Prydz, K. (2001) Internalization and Stepwise Degradation of Heparan sulfate Proteoglycans in Rat Hepatocytes. Biochimica et Biophysica Acta (BBA)—Molecular Cell Research, 1541, 135-149.
[169] Scali, C., Prosperi, C., Vannucchi, M.G., Pepeu, G. and Casamenti, F. (2000) Brain Inflammatory Reaction in an Animal Model of Neuronal Degeneration and Its Modulation by an Anti-Inflammatory Drug: Implication in Alzheimer’s Disease. European Journal of Neuroscience, 12, 1900-1912. http://dx.doi.org/10.1046/j.1460-9568.2000.00075.x
[170] Teyssier, C., Guenot, L., Suschetet, W. and Siess, M.H. (1999) Metabolism of Diallyl Disulfide by Human Liver Microsomal Cytochromes P-450 and Flavin-Containing Monooxygenases. Drug Metabolism and Disposition, 27, 835-841.
[171] López-Figueroa, M.O. and Moller, M. (1996) Nitric Oxide Synthase in the Pineal Gland. Histology and Histopathology, 11, 1089-1100.
[172] Spessert, R., Layes, E., Schollmayer, A., Reuss, S. and Vollrath, L. (1995) In the Rat Pineal Gland, but Not in the Suprachiasmatic Nucleus, the Amount of Constitutive Neuronal Nitric Oxide Synthase Is Regulated by Environmental Lighting Conditions. Biochemical and Biophysical Research Communications, 212, 70-76.
http://dx.doi.org/10.1006/bbrc.1995.1937
[173] Skwarlo-Sonta, K. (2002) Melatonin in Immunity: Comparative Aspects. Neuroendocrinology Letters, 23, 61-66.
[174] Wu, Y.H. and Swaab, D.F. (2005) The Human Pineal Gland and Melatonin in Aging and Alzheimer’s Disease. Journal of Pineal Research, 38, 145-152.
http://dx.doi.org/10.1111/j.1600-079X.2004.00196.x
[175] Romero, A., Ramos, E., de Los Ros, C., Egea, J., Del Pino, J. and Reiter, R.J. (2014) A Review of Metal-Catalyzed Molecular Damage: Protection by Melatonin. Journal of Pineal Research, 56, 343-370.
http://dx.doi.org/10.1111/jpi.12132
[176] van Rensburg, S.J., Daniels, W.M., Potocnik, F.C., van Zyl, J.M., Taljaard, J.J. and Emsley, R.A. (1997) A New Model for the Pathophysiology of Alzheimer’s Disease. Aluminium Toxicity Is Exacerbated by Hydrogen Peroxide and Attenuated by an Amyloid Protein Fragment and Melatonin. South African Medical Journal, 7, 1111-1115.
[177] Liu, R.Y., Zhou, J.N., van Heerikhuize, J., Hofman, M.A. and Swaab, D.F. (1999) Decreased Melatonin Levels in Postmortem Cerebrospinal Fluid in Relation to Aging, Alzheimer’s Disease, and Apolipoprotein E-ε4/4 Genotype. Journal of Clinical Endocrinology & Metabolism, 84, 323-327.
[178] Mahlberg, R., Walther, S., Kalus, P., Bohner, G., Haedel, S., Reischies, F.M., et al. (2008) Pineal Calcification in Alzheimer’s Disease: An in Vivo Study Using Computed tomography. Neurobiology of Aging, 29, 203-209. http://dx.doi.org/10.1016/j.neurobiolaging.2006.10.003
[179] Reiter, R.J., Tan, D.X., Manchester, L.C. and El-Sawi, M.R. (2002) Melatonin Reduces Oxidant Damage and Promotes Mitochondrial Respiration: Implications for Aging. Annals of the New York Academy of Sciences, 959, 238-250.
http://dx.doi.org/10.1111/j.1749-6632.2002.tb02096.x
[180] Maruszak, A. and Zekanowski, C. (2011) Mitochondrial Dysfunction and Alzheimer’s Disease. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 35, 320-330.
http://dx.doi.org/10.1016/j.pnpbp.2010.07.004
[181] Limson, J., Nyokong, T. and Daya, S. (1998) The Interaction of Melatonin and Its Precursors with Aluminium, Cadmium, Copper, Iron, Lead, and Zinc: An Adsorptive Voltammetric Study. Journal of Pineal Research, 24, 15-21.
http://dx.doi.org/10.1111/j.1600-079X.1998.tb00361.x
[182] Pappolla, M.A., Sos, M., Omar, R.A., Bick, R.J., Hickson-Bick, D.L.M., Reiter, R.J., et al. (1997) Melatonin Prevents Death of Neuroblastoma Cells Exposed to the Alzheimer Amyloid Peptide. The Journal of Neuroscience, 17, 1683-1690.
[183] Liu, S.J. and Wang, J.Z. (2002) Alzheimer-Like Tau Phosphorylation Induced by Wortmannin in Vivo and Its Attenuation by Melatonin. Acta Pharmacologica Sinica, 23, 183-187.
[184] Adeloye, A. and Felson, B. (1974) Incidence of Normal Pineal Gland Calcification in Skull Roentgenograms of Black and White Americans. American Journal of Roentgenology, 122, 503-507. http://dx.doi.org/10.2214/ajr.122.3.503
[185] Seneff, S., Davidson, R.M. and Liu, J. (2012) Is Cholesterol Sulfate Deficiency a Common Factor in Preeclampsia, Autism, and Pernicious Anemia? Entropy, 14, 2265-2290.
http://dx.doi.org/10.3390/e14112265
[186] Michel, J.B., Feron, O., Sacks, D. and Michel, T. (1997) Reciprocal Regulation of Endothelial Nitric-Oxide Synthase by Ca2+-Calmodulin and Caveolin. Journal of Biological Chemistry, 272, 15583-15586.
http://dx.doi.org/10.1074/jbc.272.25.15583
[187] Siegel, N. and Haug, A. (1983) Aluminum Interaction with Calmodulin. Evidence for Altered Structure and Function from Optical and Enzymatic Studies. Biochimica et Biophysica Acta (BBA)—Protein Structure and Molecular Enzymology, 744, 36-45. http://dx.doi.org/10.1016/0167-4838(83)90337-0

  
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