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

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CHAPTER 3 assume that the distinct cerebral areas exhibit different sensitivities to aluminium, which can be partly explained by the differences in the brain barrier mechanisms. In fact, our data lean towards the concept of the blood-brain regional barrier introduced by Zheng et al. (2003). Evidently, the hypothesis that it would be more accurate to talk about a blood-hippocampal barrier and a blood-striatum barrier, for example, needs to be corroborated and characterised by future research. Acknowledgments This study was supported by grants PGIDIT03PXIB20804PR (to R.S.-O.) and PGIDIT07CSA005208PR (to J.L.L.-G.) from XUGA (Santiago de Compostela, Spain), and grants SAF2007-66114 (to R.S.-O.) and BFU2006-07414 (to J.L.L.-G.) from Ministerio de Ciencia e Innovación (Madrid, Spain). 136
CHAPTER 3 Table 1. In vitro effects of the presence of aluminium on the enzyme activities of SOD, GPx, CAT, and MAO Al 3+ (�M) SOD (U) GPx (U) CAT (U) MAO (nmol 4-HQ/mg protein/min) MAO-A MAO-B control 10.8 � 0.86 1.96 � 0.194 24.7 � 1.77 1.15 � 0.077 2.19 � 0.057 10 11.2 � 0.78 2.14 � 0.131 22.8 � 0.42 1.14 � 0.054 2.15 � 0.064 50 11.3 � 0.41 2.25 � 0.115 23.4 � 1.43 1.13 � 0.083 2.17 � 0.089 100 11.0 � 0.92 2.17 � 0.257 24.0 � 2.75 1.14 � 0.095 2.16 � 0.052 SOD, GPx, and CAT activities were determined using commercial enzymes, while MAO activity (MAO-A and MAO-B) was determined using mitochondrial preparation obtained from rat brain. All the incubations were performed at 37ºC. Abbreviations: SOD, superoxide dismutase; GPx, glutathione peroxidase; CAT, catalase; MAO, monoamine oxidase; 4-HQ, 4-hydroxyquinoline. Data are expressed as means � SD from four determinations (n = 4). Significance of differences among groups was assessed by a one-way ANOVA followed by a Bonferroni‟s test. No significant differences were obtained for p < 0.05. 137
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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
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
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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 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 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 and 182: CONCLUSIONS The results obtained in
Page 183: 13) Aluminium does affect neither M
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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