Mechanisms of aluminium neurotoxicity in oxidative stress-induced ...

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CONCLUSIONS 5) Intraperitoneal aluminium chloride exposure to rats for one week causes a 158 significant and greater aluminium accumulation in cerebellum, cortex, hippocampus and striatum, whereas a decrease in aluminium concentration is reported in ventral midbrain. 6) Aluminium administered i.p. predominantly accumulates in the hippocampus, whereas aluminium administered orally principally accumulates in the ventral midbrain. 7) Aluminium accumulation in the brain and its distribution in the different areas of the brain varie with the administration route used. Chapter 3 8) Aluminium i.p. exposure to rats can create a situation of oxidative stress in most of the brain areas studied. 9) Aluminium causes a significant increase in the levels of TBARS in ventral midbrain, cortex and striatum, but particularly so in the cerebellum, while no significant changes is noted in the hippocampus. 10) Aluminium provokes a significant increase in both PCC and PTC in the cerebellum, ventral midbrain, and striatum, whereas a decrease is reported in the cortex and hippocampus. The molecular mechanism involved in the lack of a direct correlation between the increase observed in the PCC, and the “apparently” contradictory increase in PTC has not been found out. 11) All the brain regional areas examined show similar behaviour patterns as aluminium leads to a decrease of the enzyme activity of SOD, GPx, and CAT, except in hippocampus where antioxidant enzymes activities increase. 12) Aluminium does not significantly alter the enzyme activities of either of SOD, GPx, and CAT in vitro.
13) Aluminium does affect neither MAO-A nor MAO-B activity in vitro. CONCLUSIONS 14) In this experimental model of PD aluminium causes an enhancement in 6-OHDA- induced lipid peroxidation and protein oxidation in vivo, except for PTC in ventral midbrain. 15) The administration of aluminium to control rats that were given intraventricularly saline instead of 6-OHDA also causes a significant difference in the levels of both lipid peroxidation and protein oxidation for PCC. 16) Immunohistochemical studies show that aluminium administration alone causes no significant change in TH-ir striatal terminals. In contrast, lesion with 6-OHDA causes a loss of TH-ir striatal terminals, which is significantly increased with the administration of aluminium. According to the previously mentioned conclusions, we establish that the results here reported confirm the potential of aluminium as a risk factor in the development of PD. This metal acts mainly as a pro-oxidant and is able to reduce the activities of antioxidant enzymes. Its toxicity in the different brain areas studied (cerebellum, ventral midbrain, cortex, and striatum) is probably mediated by the contribution of AlO2 ●2+ and other free radical-induced oxidative cell damage. Interestingly, the results observed in the hippocampus (high aluminium content and not increased oxidant status) may be caused by specific compensatory mechanism(s) of the blood-hippocampal barrier but this idea still needs to be corroborated and characterized by future research. 159
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Universidade de Santiago de Compost
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Don Ramón Soto Otero y Doña Estef
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Acknowledgements The work of this t
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Abbreviations AA ascorbic acid AD A
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Abbreviations (continuation) PCC pr
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List of figures (continuation) Chap
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TABLE OF CONTENTS INTRODUCTION ....
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CHAPTER 3 Brain oxidative stress an
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INTRODUCTION PARKINSON’S DISEASE
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INTRODUCTION PD is found in all eth
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Bradykinesia INTRODUCTION Bradykine
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INTRODUCTION predate the occurrence
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Table 1: Differential diagnostic in
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INTRODUCTION Table 3: National Inst
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Figure 4: Dopamine catabolism (Mén
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The basal ganglia INTRODUCTION The
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The death of SNpc DAergic neurons I
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INTRODUCTION the dorsomedial part o
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INTRODUCTION characterized as are l
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INTRODUCTION (Olanow et al. 2004).
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Etiology and pathogenesis of PD INT
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Ageing INTRODUCTION Ageing remains
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INTRODUCTION The finding of MPTP to
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INTRODUCTION may clarify why many n
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Misfolding and aggregation of prote
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INTRODUCTION (E3) (Figure 18A). Los
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INTRODUCTION in connection with Par
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INTRODUCTION Oxidative damage happe
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DA metabolism as a source of ROS IN
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Contribution of oxidative and nitro
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Excitotoxicity INTRODUCTION Glutama
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INTRODUCTION al. 1996, Cicchetti et
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Experimental models of PD INTRODUCT
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INTRODUCTION induce selective DAerg
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ALUMINIUM General features INTRODUC
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INTRODUCTION Varying amounts of alu
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INTRODUCTION and antiperspirants co
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INTRODUCTION approximately 3% of al
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Excretion INTRODUCTION As insoluble
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INTRODUCTION 3.5 mg may be increase
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INTRODUCTION Oteiza 1999), non-iron
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Aluminium as a cell membrane menace
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INTRODUCTION mobilization of Ca 2+
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Aluminium impairs neurotransmission
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AIMS OF THE PRESENT THESIS The main
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OBJETIVOS
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OBJETIVOS 3) Evaluar de forma preci
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CHAPTER 1 Time-course of brain oxid
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CHAPTER 1 INTRODUCTION 86 6-OHDA (2
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CHAPTER 1 MATERIALS AND METHODS Che
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CHAPTER 1 followed by centrifugatio
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CHAPTER 1 RESULTS Effects of 6-OHDA
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CHAPTER 1 DISCUSSION 94 As shown by
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CHAPTER 1 strategies or to study th
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CHAPTER 1 Fig. 2 Changes in PCC in
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CHAPTER 2
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ABSTRACT CHAPTER 2 In the present w
Page 131 and 132: MATERIALS AND METHODS Chemicals CHA
Page 133 and 134: CHAPTER 2 atomization used were 1,5
Page 135 and 136: DISCUSSION CHAPTER 2 Aluminium ente
Page 137: Table 1. Graphite furnace programme
Page 141: CHAPTER 3 Brain oxidative stress an
Page 144 and 145: CHAPTER 3 INTRODUCTION 120 The huma
Page 146 and 147: CHAPTER 3 MATERIALS AND METHODS Che
Page 148 and 149: CHAPTER 3 1:15 for hippocampus and
Page 150 and 151: CHAPTER 3 initially incorporated to
Page 152 and 153: CHAPTER 3 RESULTS In vivo effects o
Page 154 and 155: CHAPTER 3 Effects of aluminium admi
Page 156 and 157: CHAPTER 3 DISCUSSION 132 Aluminium
Page 158 and 159: CHAPTER 3 hippocampus, showed simil
Page 160 and 161: CHAPTER 3 assume that the distinct
Page 162 and 163: CHAPTER 3 Fig. 1 Levels of TBARS (A
Page 164 and 165: CHAPTER 3 Fig. 2 Enzyme activity of
Page 166 and 167: CHAPTER 3 Fig. 3 Microphotographs s
Page 168 and 169: CHAPTER 3 Fig. 5 Levels of TBARS (A
Page 170 and 171: CHAPTER 3 Fig. 6 In vitro effects o
Page 173: SUMMARY
Page 176 and 177: SUMMARY values were attained at 48
Page 178 and 179: SUMMARY neurodegeneration in the DA
Page 181: CONCLUSIONS The results obtained in
Page 187 and 188: RESUMEN RESUMEN Desde el punto de v
Page 189 and 190: RESUMEN zonas cerebrales excepto en
Page 191: CONCLUSIONES
Page 194 and 195: CONCLUSIONES Capítulo 2 4) La admi
Page 196 and 197: CONCLUSIONES 172 En base a las conc
Page 199 and 200: Publications as a direct result fro
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