Aluminum-Induced Electrophysiological Variation, Synaptic Plasticity Impairment,
9.3 Conclusion and Future Perspectives
food to mice found that protein and mRNA levels of Ras in neurons were increased;
at the same time, the protein and mRNA levels of rafl, ERK2, and CREB were hin- dered by aluminum. Aluminum affects the brain information storage and memory via Ras/ERK signal transduction [50]. Our previous study [51] found that with the increasing aluminum dosage, a gradually decreasing RAS activity of the rat hippo- campus was produced after gradually suppressing on LTP; the RAS→PI3K/
PKB→GluR1 S831 and S845 signal transduction pathway may be involved in the inhibition of hippocampal LTP by aluminum exposure in rats.
9.2.4.5 Wnt Pathway and Aluminum Effect on Synaptic Plasticity
As we know now, Wnt1, Wnt3a, Wnt7a, and Wnt8 bind the receptor Frizzled and the LRP5/6 co-receptors, activating the Wnt/ß-catenin [52]. Both Fz and LRP5/6 recruit the protein disheveled (Dvl) usually by phosphorylation, which oligomerizes in the plasma membrane forming a platform for the allocation of the scaffold pro- tein Axin and the glycogen synthase kinase-3ß (GSK-3ß) [53, 54]. The phosphory- lation of LRP5/6 causes the inhibition of GSK-3ß and adenomatous polyposis coli (APC). The consequence of this inhibition is the cytoplasmic stabilization of ß-catenin which enters the nucleus and regulates the transcription of Wnt target genes [55]. The activation of Wnt signaling increases synaptic transmission and facilitates LTP in hippocampal brain slices and in cultured neurons, suggesting a key role for Wnt signaling in the regulation of synaptic plasticity [56, 57]. Studies have shown that long-term exposure to aluminum environment could increase the activity of GSK-3ß and then inhibit the signal transduction [58]. Our previous study found that Al-induced LTP impairment might be related to the activation of GSK-3ß [59]. Researchers found that in PC 12 cells treated with aluminum maltolate,contents of Wnt3, DVL, and ß-catenin were decreased and finally Wnt/ß-catenin pathway was weakened [60].
3. Why are there so many signaling cascade participants in the process of damage induced by Al? The cooperation between neurons and synapses is critical to understand the behavior of brain functions. Further studies are required to estab- lish the upstream activators and downstream effectors of these cascades and to answer how so many signaling cascades relate to the other signaling processes that might be involved in the Al-induced inhibition of synaptic plasticity.
References
1. Yokel RA (2000) The toxicology of aluminum in the brain: a review. Neurotoxicology 21(5):813–828
2. Goncalves PP, Silva VS (2007) Does neurotransmission impairment accompany aluminium neurotoxicity? J Inorg Biochem 101(9):1291–1338
3. McLaughlin AI et al (1962) Pulmonary fibrosis and encephalopathy associated with the inhala- tion of aluminium dust. Br J Ind Med 19:253–263
4. Crapper DR, Krishnan SS, Dalton AJ (1973) Brain aluminum distribution in Alzheimer’s dis- ease and experimental neurofibrillary degeneration. Trans Am Neurol Assoc 98:17–20 5. Chopra JS et al (1986) Aluminium phosphide poisoning: a prospective study of 16 cases in one
year. Postgrad Med J 62(734):1113–1115
6. Perl DP et al (1982) Intraneuronal aluminum accumulation in amyotrophic lateral sclerosis and Parkinsonism-dementia of Guam. Science 217(4564):1053–1055
7. Zhang L et al (2011) Effects of subchronic aluminum exposure on serum concentrations of iron and iron-associated proteins in rats. Biol Trace Elem Res 141(1–3):246–253
8. Moyer JR Jr, Thompson LT, Disterhoft JF (1996) Trace eyeblink conditioning increases CA1 excitability in a transient and learning-specific manner. J Neurosci Off J Soc Neurosci 16(17):5536
9. Oh MM et al (2003) Watermaze learning enhances excitability of CA1 pyramidal neurons.
J Neurophysiol 90(4):2171–2179
10. Saar D, Grossman Y, Barkai E (2001) Long-lasting cholinergic modulation underlies rule learning in rats. J Neurosci Off J Soc Neurosci 21(4):1385
11. Suarez-Fernandez MB et al (1999) Aluminum-induced degeneration of astrocytes occurs via apoptosis and results in neuronal death. Brain Res 835(2):125–136
12. Deloncle R et al (2001) Ultrastructural study of rat hippocampus after chronic administration of aluminum L-glutamate: an acceleration of the aging process. Exp Gerontol 36(2):231–244 13. Blaustein MP, Goldman DE (1968) The action of certain polyvalent cations on the voltage-
clamped lobster axon. J Gen Physiol 51(3):279–291
14. Shaw CA, Tomljenovic L (2013) Aluminum in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and autoimmunity. Immunol Res 56(2–3):304–316 15. Saar D, Barkai E (2009) Long-lasting maintenance of learning-induced enhanced neuronal
excitability: mechanisms and functional significance. Mol Neurobiol 39(3):171–177 16. Malenka RC, Bear MF (2004) LTP and LTD: an embarrassment of riches. Neuron 44(1):5–21 17. Kawahara M, Katonegishi M (2011) Link between aluminum and the pathogenesis of
Alzheimer’s disease: the integration of the aluminum and amyloid cascade hypotheses. Int J Alzheimers Dis 2011(2):276393
18. Schreurs BG et al (1998) Intracellular correlates of acquisition and long-term memory of classical conditioning in Purkinje cell dendrites in slices of rabbit cerebellar lobule HVI. J Neurosci 18(14):5498–5507
19. Alkon DL et al (1998) Time domains of neuronal Ca2+ signaling and associative memory: steps through a calexcitin, ryanodine receptor, K+ channel cascade. Trends Neurosci 21(12):529
20. McCrohan CR et al (2000) Bioaccumulation and toxicity of aluminium in the pond snail at neutral pH. Acta Biol Hung 51(2–4):309–316
21. Platt B et al (1995) Aluminum impairs hippocampal long-term potentiation in rats in vitro and in vivo. Exp Neurol 134(1):73–86
22. Koenig ML, Jope RS (1987) Aluminum inhibits the fast phase of voltage-dependent calcium influx into synaptosomes. J Neurochem 49(1):316–320
23. D’Almeida V et al (1995) Antioxidant defense in rat brain after chronic treatment with anorec- tic drugs. Toxicol Lett 81(2–3):101–105
24. Julka D, Gill KD (1996) Altered calcium homeostasis: a possible mechanism of aluminium- induced neurotoxicity. Biochim Biophys Acta 1315(1):47–54
25. Kauer JA, Malenka RC, Nicoll RA (1988) A persistent postsynaptic modification mediates long-term potentiation in the hippocampus. Neuron 1(10):911–917
26. Bliss TVP, Collingridge GL (1993) Asynaptic model of memory: long-term potentiation in the hippocampus. Nature 361(6407):31–39
27. Mclachlan DR et al (1991) Would decreased aluminum ingestion reduce the incidence of Alzheimer’s disease? CMAJ 145(7):793–804
28. Yokel RA (1994) Aluminum exposure produces learning and memory deficits. Springer, New York, pp 301–318
29. Platt B, Reymann KG (1996) Inhibition of TEA-induced LTP by aluminum. Exp Neurol 141(2):240–247
30. Wang M et al (2001) Vasopressin reverses aluminum-induced impairment of synaptic plastic- ity in the rat dentate gyrus in vivo. Brain Res 899(1–2):193
31. Wang M et al (2002) The influence of developmental period of aluminum exposure on synaptic plasticity in the adult rat dentate gyrus in vivo. Neuroscience 113(2):411–419
32. Liang RF et al (2012) Aluminium-maltolate-induced impairment of learning, memory and hippocampal long-term potentiation in rats. Ind Health 50(5):428–436
33. Song J et al (2014) Effects of exposure to aluminum on long-term potentiation and AMPA receptor subunits in Rats in vivo. 生物医学与环境科学 27(2):77–84
34. Jourdain P et al (2002) Remodeling of hippocampal synaptic networks by a brief anoxia- hypoglycemia. J Neurosci 22(8):3108–3116
35. Kandel ER (2001) NOBEL LECTURE: the molecular biology of memory storage: a dialog between genes and synapses. Biosci Rep 21:565–611. Portland Press Ltd
36. Montarolo PG et al (1986) A critical period for macromolecular synthesis in long-term hetero- synaptic facilitation in Aplysia. Science 234(4781):1249–1254
37. Hatada Y et al (2006) Calmodulin and Ca2+and calmodulin dependent protein kinase in rat anterior pituitary gland. J Neurochem 40(4):1082–1089
38. Cooke SF, Bliss TV (2006) Plasticity in the human central nervous system. Brain 129(Pt 7):1659
39. Ulusoy HB et al (2015) Intraperitoneal administration of low dose aluminium in the rat: how good is it to produce a model for Alzheimer disease. Arch Ital Biol 153(4):266–278
40. Canales JJ et al (2001) Aluminium impairs the glutamate-nitric oxide-cGMP pathway in cul- tured neurons and in rat brain in vivo: molecular mechanisms and implications for neuropa- thology. J Inorg Biochem 87(1):63–69
41. Tüzmen MN et al (2015) Effects of curcumin and tannic acid on the aluminum- and lead- induced oxidative neurotoxicity and alterations in NMDA receptors. Toxicol Mech Methods 25(2):120–127
42. Wang B et al (2014) Disturbance of intracellular calcium homeostasis and CaMKII/CREB signaling is associated with learning and memory impairments induced by chronic aluminum exposure. Neurotox Res 26(1):52–63
43. Wang B, Zhao XY, Deng X (2010) Effects of chronic aluminum exposure on memory through multiple signal transduction pathways. Environ Toxicol Pharmacol 29(3):308
44. Iglesias-González J et al (2017) Effects of aluminium on rat brain mitochondria bioenergetics:
an in vitro and in vivo study. Mol Neurobiol 54(1):563–570
45. Moraes TP et al (2010) Low-calcium peritoneal dialysis solution is effective in bringing PTH levels to the range recommended by current guidelines in patients with PTH levels < 150 pg/
dL. J Bras Nefrol 32(3):275
46. Beers GT (2001) Mitogen-activated protein (MAP) kinase pathways: regulation and physi- ological functions. Endocr Rev 22(2):153
47. Liu MG et al (2011) Differential roles of ERK, JNK and p38 MAPK in pain-related spatial and temporal enhancement of synaptic responses in the hippocampal formation of rats: multi- electrode array recordings. Brain Res 1382(9):57
48. Thomas GM, Huganir RL (2004) MAPK cascade signalling and synaptic plasticity. Nat Rev Neurosci 5(3):173
49. Cui X et al (2012) The effects of chronic aluminum exposure on learning and memory of rats by observing the changes of Ras/Raf/ERK signal transduction pathway. Food Chem Toxicol 50(2):315
50. Sakamoto K, Karelina K, Obrietan K (2011) CREB: a multifaceted regulator of neuronal plas- ticity and protection. J Neurochem 116(1):1
51. Song J et al (2016) The RAS/PI3K pathway is involved in the impairment of long-term poten- tiation induced by acute aluminum treatment in rats. 生物医学与环境科学 29(11):782–789 52. Sangtaek O (2012) Identification of antimycin A as a small molecule inhibitor of the Wnt/β- -
catenin pathway. Bull Kor Chem Soc 33
53. Schweizer L, Varmus H (2003) Wnt/wingless signaling through beta-catenin requires the func- tion of both LRP/arrow and frizzled classes of receptors. BMC Cell Biol 4(1):4
54. Schwarz-Romond T et al (2007) The DIX domain of dishevelled confers Wnt signaling by dynamic polymerization. Nat Struct Mol Biol 14(6):484
55. Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20(20):781
56. Budnik V, Salinas PC (2011) Wnt signaling during synaptic development and plasticity. Curr Opin Neurobiol 21(1):151
57. Varelanallar L et al (2010) Wingless-type family member 5A (Wnt-5a) stimulates syn- aptic differentiation and function of glutamatergic synapses. Proc Natl Acad Sci U S A 107(49):21164–21169
58. Scali C et al (2006) Inhibition of Wnt signaling, modulation of Tau phosphorylation and induc- tion of neuronal cell death by DKK1. Neurobiol Dis 24(2):254
59. Zhang H et al (2016) Caspase-3 is involved in aluminum-induced impairment of long-term potentiation in rats through the Akt/GSK-3β pathway. Neurotox Res 29(4):484–494
60. Li WQ (2012) Wnt/beta-catenin pathway on the apoptosis of PC-12 cells induced by maltol aluminum. Shanxi Medical University
173
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