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

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INTRODUCTION Figure 13: Six stages of brain pathology in idiopathic PD (Braak et al. 2003) Figure 14: Stages 3–6 of pathological changes associated with sporadic PD in hemisphere sections immunostained for �-synuclein (Braak et al. 2006) 24
Etiology and pathogenesis of PD INTRODUCTION The cause of most cases of PD remains unclear. By the date several pathogenic mechanisms based on environmental, genetic and histopathological findings have been implicated in this disease. They may be primary activating events for the disease and secondary events involved in promoting progression of PD over time. The contributions of genetic and environmental risk factors and the impact of compensatory mechanisms on PD progression are still unanswered questions. Some forms of PD have been associated to specific environmental causes (Langston et al. 1983, Thrash et al. 2007, Jang et al. 2008), while a few familial forms of PD and related parkinsonism are related to apparent genetic causes (Biskup et al. 2008, Gasser 2009). Genetics of PD In the majority of PD cases, there is no apparent genetic linkage and the disease is referred to as “sporadic” or idiopathic PD. Thus, familial cases only represent a 5- 10% of the whole affected population. The disease is inherited and defined by at least one relative (parent or sibling) also having PD. It is not always clear if this is due to heritable genetic factors or shared environment. But an inherited genetic contribution was put forward by various studies, mono- and dizygotic twins and families with PD history (Tanner 1999, Thacker and Ascherio 2008). An increasing number of single gene mutations causing familial PD have been identified (Table 4). They show both autosomal dominant and recessive as well as X- linked modes of inheritance (Vila and Przedborski 2004, Wood-Kaczmar et al. 2006). Many of these have also been found in apparently sporadic cases (Warner and Schapira 2003) suggesting that they may act as susceptibility factors. Chromosomal regions have been designated as “PARK” genes. These include two autosomal dominant genes: �- synuclein (SNCA) (Polymeropoulos et al. 1997, Krüger et al. 1998) and leucine-rich repeat kinase 2 LRRK2 (Paisán-Ruiz et al. 2004, Zimprich et al. 2004), and three autosomal recessive genes: parkin (PRKN) (Kitada et al. 1998), PTEN-induced putative 25
Page 1: Universidade de Santiago de Compost
Page 5: Don Ramón Soto Otero y Doña Estef
Page 9 and 10: Acknowledgements The work of this t
Page 11 and 12: Abbreviations AA ascorbic acid AD A
Page 13: Abbreviations (continuation) PCC pr
Page 16 and 17: List of figures (continuation) Chap
Page 19 and 20: TABLE OF CONTENTS INTRODUCTION ....
Page 21: CHAPTER 3 Brain oxidative stress an
Page 25 and 26: INTRODUCTION PARKINSON’S DISEASE
Page 27 and 28: INTRODUCTION PD is found in all eth
Page 29 and 30: Bradykinesia INTRODUCTION Bradykine
Page 31 and 32: INTRODUCTION predate the occurrence
Page 33 and 34: Table 1: Differential diagnostic in
Page 35 and 36: INTRODUCTION Table 3: National Inst
Page 37 and 38: Figure 4: Dopamine catabolism (Mén
Page 39 and 40: The basal ganglia INTRODUCTION The
Page 41 and 42: The death of SNpc DAergic neurons I
Page 43 and 44: INTRODUCTION the dorsomedial part o
Page 45 and 46: INTRODUCTION characterized as are l
Page 47: INTRODUCTION (Olanow et al. 2004).
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
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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
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MATERIALS AND METHODS Chemicals CHA
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CHAPTER 2 atomization used were 1,5
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DISCUSSION CHAPTER 2 Aluminium ente
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Table 1. Graphite furnace programme
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CHAPTER 3 Brain oxidative stress an
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CHAPTER 3 INTRODUCTION 120 The huma
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CHAPTER 3 MATERIALS AND METHODS Che
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CHAPTER 3 1:15 for hippocampus and
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CHAPTER 3 initially incorporated to
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CHAPTER 3 RESULTS In vivo effects o
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CHAPTER 3 Effects of aluminium admi
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CHAPTER 3 DISCUSSION 132 Aluminium
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CHAPTER 3 hippocampus, showed simil
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CHAPTER 3 assume that the distinct
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CHAPTER 3 Fig. 1 Levels of TBARS (A
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CHAPTER 3 Fig. 2 Enzyme activity of
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CHAPTER 3 Fig. 3 Microphotographs s
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CHAPTER 3 Fig. 5 Levels of TBARS (A
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CHAPTER 3 Fig. 6 In vitro effects o
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SUMMARY
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SUMMARY values were attained at 48
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SUMMARY neurodegeneration in the DA
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CONCLUSIONS The results obtained in
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13) Aluminium does affect neither M
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RESUMEN RESUMEN Desde el punto de v
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RESUMEN zonas cerebrales excepto en
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CONCLUSIONES
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CONCLUSIONES Capítulo 2 4) La admi
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CONCLUSIONES 172 En base a las conc
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Publications as a direct result fro
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REFERENCES
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Page 274:
REFERENCES Zhou W., Zhu M., Wilson
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