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

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ABSTRACT CHAPTER 3 The ability of aluminium to affect the oxidant status of specific areas of the brain (cerebellum, ventral midbrain, cortex, hippocampus, striatum) was investigated in male Sprague-Dawley rats intraperitoneally treated with aluminium chloride (10 mg Al 3+ /kg/day) for ten days. The potential of aluminium to act as an etiological factor in PD was assessed by studying its ability to increase oxidative stress in ventral midbrain and striatum and the striatal DAergic neurodegeneration induced by 6-OHDA administered intraventricularly in an experimental model of PD. The results showed that aluminium caused an increase in oxidative stress (TBARS, PCC, and PTC) for most of the brain regions studied, which was accompanied by a decrease in the activity of some antioxidant enzymes (SOD, CAT, GPx). However, studies in vitro confirmed the inability of aluminium to affect the activity of those enzymes. The reported effects exhibited a regional-selective behaviour for all the cerebral structures studied. Aluminium also enhanced the ability of 6-OHDA to cause oxidative stress and neurodegeneration in the DAergic system, which confirms its potential as a risk factor in the development of PD. Keywords: 6-hydroxydopamine, aluminium, antioxidant enzymes, lipid peroxidation, Parkinson‟s disease, protein oxidation. 119
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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
Page 91 and 92: Aluminium as a cell membrane menace
Page 93 and 94: INTRODUCTION mobilization of Ca 2+
Page 95: Aluminium impairs neurotransmission
Page 99 and 100: AIMS OF THE PRESENT THESIS The main
Page 101: OBJETIVOS
Page 104 and 105: OBJETIVOS 3) Evaluar de forma preci
Page 107: CHAPTER 1 Time-course of brain oxid
Page 110 and 111: CHAPTER 1 INTRODUCTION 86 6-OHDA (2
Page 112 and 113: CHAPTER 1 MATERIALS AND METHODS Che
Page 114 and 115: CHAPTER 1 followed by centrifugatio
Page 116 and 117: CHAPTER 1 RESULTS Effects of 6-OHDA
Page 118 and 119: CHAPTER 1 DISCUSSION 94 As shown by
Page 120 and 121: CHAPTER 1 strategies or to study th
Page 122 and 123: CHAPTER 1 Fig. 2 Changes in PCC in
Page 125: CHAPTER 2
Page 129 and 130: 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 145 and 146: CHAPTER 3 not undergo redox reactio
Page 147 and 148: CHAPTER 3 saline over the same peri
Page 149 and 150: CHAPTER 3 used as chemical dosimete
Page 151 and 152: Statistical analysis CHAPTER 3 Data
Page 153 and 154: CHAPTER 3 was noted in hippocampus
Page 155 and 156: CHAPTER 3 In vitro effects of alumi
Page 157 and 158: CHAPTER 3 administration routes (De
Page 159 and 160: CHAPTER 3 difference in the levels
Page 161 and 162: CHAPTER 3 Table 1. In vitro effects
Page 163 and 164: CHAPTER 3 139
Page 167 and 168: CHAPTER 3 Fig. 4 Density of striata
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Page 175 and 176: SUMMARY SUMMARY Aluminium has becom
Page 177 and 178: SUMMARY stress is reached at this t
Page 179: CONCLUSIONS
Page 182 and 183: CONCLUSIONS 5) Intraperitoneal alum
Page 185: RESUMEN
Page 188 and 189: RESUMEN 1996, Shimohama et al. 2003
Page 190 and 191: RESUMEN 166 Por último y con el fi
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CONCLUSIONES CONCLUSIONES Los resul
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CONCLUSIONES aumento de grupos carb
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APPENDIX
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APPENDIX Publications arising from
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