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The aluminum-induced increase in blood-brain barrier permeability to delta-sleep-inducing peptide occurs throughout the brain and is independent of phosphorus and acetylcholinesterase levels

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Abstract

The effect of aluminum on levels of inorganic phosphorus and acetylcholinesterase in blood and brain and on permeability of the blood-brain barrier (BBB) in different regions of the brain to the neuropeptide deltasleep-inducing peptide (DSIP) was studied in adult rats. Aluminum (100 mg/kg) significantly increased the permeability of the BBB to intracarotid 125I-N-Tyr-DSIP so that levels of radioactivity in whole brain were 45% higher than in control animals. The pattern of regional distribution of radioactivity in the brain was, however, unaffected, demonstrating that the affect of aluminum occurs throughout the BBB. Aluminum also significantly decreased inorganic phosphorus levels in the serum by 19%, but this effect did not correlate with BBB permeability to DSIP. Aluminum did not decrease brain levels of phosphorus despite the drop in blood levels of phosphorus nor affect brain or blood levels of acetylcholinesterase. Experiments with radioactive 32P reinforced the finding that blood but not brain levels of phosphorus are reliably affected by aluminum. The lack of correlation between changes in BBB permeability and decreased levels of inorganic phosphorus in the blood suggests that the effect of aluminum may not be mediated by its effects on phosphorus metabolism. Also, the change in BBB permeability after administration of aluminum does not appear to depend on changes in brain cholinergic activity but does occur throughout the brain.

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References

  • Alafuzoff I, Adolfsson R, Bucht G, Winbland B (1983) Albumin and immunoglobulin in plasma and cerebrospinal fluid, and blood-cerebrospinal fluid barrier function in patients with dementia of Alzheimer type and multi-infarct dementia. J Neurol Sci 60:465–472

    Google Scholar 

  • Banks WA, Kastin AJ (1983a) Aluminium increases permeability of the blood-brain barrier to labelled DSIP and β-endorphin: Possible implications for senile and dialysis dementia. Lancet ii:1227–1229

    Google Scholar 

  • Banks WA, Kastin AJ (1983b) CSF-plasma relationships for DSIP and some other neuropeptides. Pharmacol Biochem Behav 19:1037–1040

    Google Scholar 

  • Banks WA, Kastin AJ (1984) Aluminum alters blood-brain barrier permeability to some non-peptides. Neuropharmacology

  • Banks WA, Kastin AJ, Coy DH (1982) Delta sleep-inducing peptide crosses the blood-brain barrier in dogs: Some correlations with protein binding. Pharmacol Biochem Behav 17:1009–1014

    Google Scholar 

  • Banks WA, Kastin AJ, Coy DH (1984) Evidence that 125I-N-Tyr-delta-sleep-inducing peptide crosses the blood-brain barrier by a non-competitive mechanism. Brain Res 301:201–207

    Google Scholar 

  • Begley DJ, Davson H, Michaelson IA (1980) Clearance of the dipeptides glycl-1-leucine from rabbit cerebrospinal fluid. J Physiol 307:83

    Google Scholar 

  • Biorksten JA (1982) Aluminum as a cause of senile dementia. Compr Ther 8:73–76

    Google Scholar 

  • Bowdler NC, Beasley DS, Fritze EC, Goulette AM, Hatton JD, Hession J (1979) Behavioral effects of aluminum ingestion on animal and human subjects. Pharmacol Biochem Behav 10:505–512

    Google Scholar 

  • Bowen DM (1979) Neurochemical findings in Alzheimer's disease. In: Glen AI, Whalley LJ (eds) Alzheimer's disease: Early recognition of potentially reversible deficits. Churchill Livingstone, New York, pp 17–26

    Google Scholar 

  • Caster WO, Wang M (1981) Dietary aluminum and Alzheimer's disease—A review. Sci Total Environ 17:31–36

    Google Scholar 

  • Commissaris RL, Cordon JJ, Sprague S, Keiser J (1982) Behavioral changes in rats after chronic aluminum and parathyroid hormone administration. Neurobehav Toxicol Teratol 4:403–410

    Google Scholar 

  • Crapper DR, Quittkat S, Krishnan SS, Dalton AJ, De Boni U (1980) Intranuclear aluminum content in Alzheimer's disease, dialysis encephalopathy, and experiment aluminum enephalopathy. Acta Neuropathol 50:19–24

    Google Scholar 

  • De Boni U, Crapper McLachlan DR (1980) Senile dementia and Alzheimer's disease: A current view. Life Sci 27:1–14

    Google Scholar 

  • Demetriou JA, Drewes PA, Gin JB (1974) Enzymes. In: Henry RJ, Cannon DC, Winkelman JW (eds) Clincal chemistry: Principles and techniques. Harper and Row, Hagestown, MD, pp 917–922

    Google Scholar 

  • Domer FR, Boerthe SB, Bing EG, Reddix I (1983) Histamine- and acetylcholine-induced changes in the permeability of the blood-brain barrier of normotensive and spontaneously hypertensive rats. Neuropharmacology 22:615–619

    Google Scholar 

  • Heald PJ (1960) Phosphorus metabolism of brain. Pergamon, New York, pp 15–19

    Google Scholar 

  • Hindfeld B, Olsson JE (1980) Soluble brain proteins in dialysis encephalopathy. Acta Neuropathol 50:241–244

    Google Scholar 

  • Houghten RA, Swann RW, Li CH (1980) β-Endorphin: Stability, clearance, behavior, and entry into the central nervous system after intravenous injection of the tritiated peptide in rats and rabbits. Proc Natl Acad Sci 77:4588–4591

    Google Scholar 

  • Kastin AJ, Nissen C, Nikolics K, Medzibradszky K, Coy DH, Teplan I, Schally AV (1976) Distribution of 3H-α-MSH in rat brain. Brain Res Bull 1:19–26

    Google Scholar 

  • Kastin AJ, Olson RD, Schally AV, Coy DH (1979) CNS effects of peripherally administered brain peptides. Life Sci 25:401–414

    Google Scholar 

  • Kastin AJ, Olson GA, Sandman CA, Ehrensing RH (1981) Possible role of peptides in senile dementia. In: Crook T, Gershon S (eds) Strategies for the possible role of peptides in senile dementia. Mark Powley Associates, New Canaan, CN, pp 139–152

    Google Scholar 

  • Kastin AJ, Banks WA, Castellanos PF, Nissen C, Coy DH (1982) Differential penetration of DSIP peptides into rat brain. Pharmacol Biochem Behav 17:1187–1191

    Google Scholar 

  • Kastin AJ, Banks WA, Zadina JE, Graf MV (1983) Brain peptides: The dangers of constricted nomenclatures. Life Sci 32:295–301

    Google Scholar 

  • King SW, Savory J, Willis MR (1981) The clinical biochemistry of aluminum. CRC Crit Rev Clin Lab Sci 14:1–20

    Google Scholar 

  • Kosik KS, Bradley WG, Good PF, Rasool CG, Selkoe DJ (1983) Cholinergic function in lumbar aluminum myelopathy. J Neuropathol Exp Neurol 42:365–375

    Google Scholar 

  • Li CH, Geschwind I, Evans HM (1949) The effect of growth hormone on the inorganic phosphorus levels in the plasma. Endocrinology 44:67–70

    Google Scholar 

  • Lotz M, Zisman E, Bartter FC (1968) Evidence for a phosphorusdepletion syndrome in man. N Engl J Med 278:409–415

    Google Scholar 

  • Marquis JK (1983) Aluminum inhibition of human serum cholinesterase. Bull Environ Contam Toxicol 31:164–169

    Google Scholar 

  • Merin M, Hollt V, Przewlocki R, Herz A (1980) Low permeation of systematically administered human β-endorphin into rabbit brain measured by radio-immunoassays differentiating human and rabbit β-endorphin. Life Sci 27:281–289

    Google Scholar 

  • Miller CA, Levine EM (1974) Effects of aluminum salts on cultured neuroblastoma cells. J Neurochem 22:751–758

    Google Scholar 

  • Nitsch C, Klatzo I (1983) Regional patterns of blood-brain barrier breakdown during epileptiform seizures induced by various convulsive agents. J Neurol Sci 59:305–322

    Google Scholar 

  • Ostman DL, Rugg DJ, Schmittdiel CJ

  • Perl DP, Gajdusek C, Garruto RM, Yanagihara T, Gibbs CJ (1982) Intraneuronal aluminum accumulation in amyotrophic lateral sclerosis and Parkinsonism dementia of Guam. Science 217:1053–1055

    Google Scholar 

  • Perry EK (1979) Correlations between psychiatric, neuropathological and biochemical findings in Alzheimer's disease. In: Glen AI, Whalley LJ (eds) Alzheimer's disease: Early recognition of potentially reversible deficits. Churchill Livingstone, NY, pp 27–32

    Google Scholar 

  • Pierides AM, Ward MK, Kerr DNS (1976) Haemodialysis encephalopathy: Possible role of phosphate depletion. Lancet i:1234–1235

    Google Scholar 

  • Rabe A, Lee MH, Shek J, Wisniewski HM (1982) Learning deficit in immature rabbits with aluminum-induced neurofibrillary changes. Exp Neurol 76:441–446

    Google Scholar 

  • Rapoport SI (1976) Blood-brain barrier in physiology and medicine. Raven, New York, pp 79–80

    Google Scholar 

  • Rapoport SI, Klee WA, Pettigrew KD, Ohno K (1980) Entry of opioid peptides into the central nervous system. Science 207:84–86

    Google Scholar 

  • Reisberg B, Ferris SH, Anand R, Mir P, Geibel V, De Leon MJ (1983) Effects of naloxone in senile dementia: A double-blind trial. N Engl J Med 308:721–722

    Google Scholar 

  • Roberts E (1981) A speculative consideration on the neurobiology and treatment of senile dementia. In: Crook T, Gershon S (eds) Strategies for the development of an effective treatment fors senile dementia. Mark Powley Associates New Canaan CN, pp 247–320

    Google Scholar 

  • Shore D, Wyatt RJ (1983) Aluminum and Alzheimer's disease. J Nerv Ment Dis 171:553–558

    Google Scholar 

  • Sideman S, Manor D (1982) The dialysis dementia syndrome and aluminum intoxication. Nephron 31:1–10

    Google Scholar 

  • Spencer H, Lender M (1979) Adverse effects of aluminum-containing antacids on mineral metabolism. Gastroenterology 76:603–606

    Google Scholar 

  • Thurston H, Gilmore GR, Swales JD (1972) Aluminum retention and toxicity in chronic renal failure. Lancet i:881–883

    Google Scholar 

  • Wallwork JC, Milne DB, Sims RL, Sandstead HH (1983) Severe zinc deficiency: Effects on the distribution of nine elements (potassium, phosphorus, sodium, magnesium, calcium, iron, zinc, copper, and manganese) in regions of the rat brain. J Nutr 113:1895–1905

    Google Scholar 

  • Wisniewski HM, Kozlowski PB (1982) Evidence for blood-brain barrier changes in senile dementia of the Alzheimer type (SDAT). Ann NY Acad Sci 396:119–129

    Google Scholar 

  • Woods SC, Porte D Jr (1977) Relationship between plasma and cerebrospinal fluid insulin levels of dogs. Am J Physiol 233:E331-E334

    Google Scholar 

  • Yates CM (1979) Aluminum and Alzheimer's disease. In: Glen AI, Whalley LJ (eds) Alzheimer's disease: Early recognition of potentially reversible deficits. Churchill Livingstone New York, pp 27–32

    Google Scholar 

  • Yokel RA (1983) Repeated systemic aluminum exposure effects on classical conditioning of the rabbit. Neurobehav Toxicol Teratol 5:41–46

    Google Scholar 

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Banks, W.A., Kastin, A.J. The aluminum-induced increase in blood-brain barrier permeability to delta-sleep-inducing peptide occurs throughout the brain and is independent of phosphorus and acetylcholinesterase levels. Psychopharmacology 86, 84–89 (1985). https://doi.org/10.1007/BF00431689

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  • DOI: https://doi.org/10.1007/BF00431689

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