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

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ABSTRACT CHAPTER 1 The unilateral and intrastriatal injection of 6-OHDA is commonly used to provide a partial lesion model of PD in the investigation of the molecular mechanisms involved in its pathogenesis and to assess new neuroprotective treatments. Its capacity to induce neurodegeneration has been related to its ability to undergo autoxidation in the presence of oxygen and consequently to generate oxidative stress. The aim of the present study was to investigate the time course of brain oxidative damage induced by 6-OHDA (6 μg in 5 μl of sterile saline containing 0.2% ascorbic acid) injection in the right striatum of male Sprague-Dawley rat. The results of this study show that the indices of both lipid peroxidation (TBARS) and protein oxidation (PCC and PTC) increase simultaneously in the ipsilateral striatum and ventral midbrain, reaching a peak value at 48-h post-injection for both TBARS and PCC, and at 24 h for PTC. A lower but significant increase was also observed in the contralateral side (striatum and ventral midbrain). The indices of oxidative stress returned to values close to those found in controls at 7-day postinjection. These data show that the oxidative stress is a possible triggering factor for the neurodegenerative process and the retrograde neurodegeneration observed after the first week post-injection seems to be a consequence of the cell damage caused during the first days post-injection. Finally, the optimal time to assess brain indices of oxidative stress (TBARS, PCC and PTC) in this model is 48-h post-injection. Keywords: Parkinson‟s disease, 6-hydroxydopamine, oxidative damage, lipid peroxidation, protein oxidation. 85
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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
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 104 and 105: OBJETIVOS 3) Evaluar de forma preci
Page 107: CHAPTER 1 Time-course of brain oxid
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
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
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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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