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

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OBJETIVOS DE LA PRESENTE TESIS OBJETIVOS Los objetivos principales de esta tesis fueron distribuidos en tres capítulos de la siguiente manera: Capítulo 1 El primer objetivo principal es determinar la cinética de las lesiones oxidativas producidas en un modelo experimental de Parkinson con 6-OHDA y cuantificar los efectos oxidativos resultantes. Este estudio nos permitirá establecer el tiempo exacto después de la inyección con 6-OHDA en el que estudiar los efectos oxidativos del aluminio. Los objetivos concretos son: 1) Analizar el curso temporal del daño oxidativo causado por la administración unilateral e intrastriatal de 6-OHDA (6 µg en 5 µl de salino estéril con 0.2% ácido ascórbico) en los lados ipsilaterales y contralaterales del estriado y mesencéfalo ventral de la rata. 2) Cuantificar los cambios observados en los níveles de peroxidación lipídica (TBARS) y del estado oxidativo de las proteínas (contenidos de grupos carbonilo y tiol en proteínas) durante el curso temporal del daño oxidativo cerebral inducido por la inyección de 6-OHDA en el modelo experimental de la enfermedad de Parkinson mencionado anteriormente. Capítulo 2 El segundo objetivo principal consiste en elaborar un régimen de dosis en el que se garantice una acumulación significativa de aluminio en el cerebro y establecer la distribución exacta del metal en las regiones cerebrales de las ratas. En este caso, el objetivo concreto es: 79
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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
Page 51 and 52: Ageing INTRODUCTION Ageing remains
Page 53 and 54: INTRODUCTION The finding of MPTP to
Page 55 and 56: INTRODUCTION may clarify why many n
Page 57 and 58: Misfolding and aggregation of prote
Page 59 and 60: INTRODUCTION (E3) (Figure 18A). Los
Page 61 and 62: INTRODUCTION in connection with Par
Page 63 and 64: INTRODUCTION Oxidative damage happe
Page 65 and 66: DA metabolism as a source of ROS IN
Page 67 and 68: Contribution of oxidative and nitro
Page 69 and 70: Excitotoxicity INTRODUCTION Glutama
Page 71 and 72: INTRODUCTION al. 1996, Cicchetti et
Page 73 and 74: Experimental models of PD INTRODUCT
Page 75 and 76: INTRODUCTION induce selective DAerg
Page 77 and 78: ALUMINIUM General features INTRODUC
Page 79 and 80: INTRODUCTION Varying amounts of alu
Page 81 and 82: INTRODUCTION and antiperspirants co
Page 83 and 84: INTRODUCTION approximately 3% of al
Page 85 and 86: Excretion INTRODUCTION As insoluble
Page 87 and 88: INTRODUCTION 3.5 mg may be increase
Page 89 and 90: 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 105: CHAPTER 1
Page 109 and 110: ABSTRACT CHAPTER 1 The unilateral a
Page 111 and 112: CHAPTER 1 2001), particularly due t
Page 113 and 114: Brain samples CHAPTER 1 After decap
Page 115 and 116: Statistical analysis CHAPTER 1 Resu
Page 117 and 118: CHAPTER 1 the left striatum and +11
Page 119 and 120: CHAPTER 1 against degeneration (Tro
Page 121 and 122: CHAPTER 1 Fig. 1 Changes in TBARS l
Page 123: CHAPTER 1 Fig. 3 Changes in PTC in
Page 127: CHAPTER 2 Analysis of brain regiona
Page 130 and 131: CHAPTER 2 INTRODUCTION 106 Aluminiu
Page 132 and 133: CHAPTER 2 experimental period of fo
Page 134 and 135: CHAPTER 2 RESULTS Aluminium distrib
Page 136 and 137: CHAPTER 2 significant increase of t
Page 139: CHAPTER 3
Page 143 and 144: ABSTRACT CHAPTER 3 The ability of a
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
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CHAPTER 3 was noted in hippocampus
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CHAPTER 3 In vitro effects of alumi
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CHAPTER 3 administration routes (De
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CHAPTER 3 difference in the levels
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CHAPTER 3 Table 1. In vitro effects
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CHAPTER 3 139
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CHAPTER 3 141
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CHAPTER 3 Fig. 4 Density of striata
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CHAPTER 3 145
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CHAPTER 3 147
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SUMMARY SUMMARY Aluminium has becom
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SUMMARY stress is reached at this t
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CONCLUSIONS
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CONCLUSIONS 5) Intraperitoneal alum
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RESUMEN
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RESUMEN 1996, Shimohama et al. 2003
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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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