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

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CHAPTER 3 RESULTS In vivo effects of aluminium administration on brain lipid peroxidation and protein oxidation 128 Lipid peroxidation was assessed by the determination of TBARS concentration, and protein oxidation was estimated by both PCC and PTC. As shown in Fig. 1A, animals exposed to aluminium (10 mg Al 3+ /kg/day for 10 days) exhibited a significant increase in lipid peroxidation in the regions of cerebellum (+159%), ventral midbrain (+54%), cortex (+20%) and striatum (+33%), while there were no significant changes in hippocampus. TBARS levels in the striatum were particularly high when compared with those found in other cerebral regions and in both aluminium-treated and control rats. Following aluminium treatment, both PCC (Fig. 1B) and PTC (Fig. 1C) were significantly elevated as compared to controls in cerebellum (+26%, +19%, respectively), ventral midbrain (+135%, +15%, respectively) and striatum (+26%, +16%, respectively), while there was a significant decrease in the cortex region (–12%, –16%, respectively) and in the hippocampus (–20%, –26%, respectively). When compared to other areas of non treated animals, PCC and PTC control levels were significantly higher in cerebral cortex and lower in the ventral midbrain (Figs. 1B and 1C). In vivo effects of aluminium administration on the brain activity of different antioxidant enzymes The effects of aluminium administration (10 mg Al 3+ /kg/day for 10 days) on the activity of different antioxidant enzymes (SOD, GPx, CAT) were also studied in several brain regions, and the results showed that the i.p. administration of aluminium influenced SOD activity (Fig. 2A). Thus, there was a significant decrease in cerebellum (–26%) and cortex (–21%) of the aluminium-treated group, while a significant increase
CHAPTER 3 was noted in hippocampus (+22%). No significant changes were detected in ventral midbrain and striatum as compared with the controls. As depicted in Fig. 2B, exposure to aluminium caused depletion in the activity of GPx in cerebellum (–26%), ventral midbrain (–28%), cortex (–28%), and striatum (–11%). By contrast, GPx activity increased in the hippocampus (+40%). Exposure of rats to aluminium decreased the levels of CAT activity (Fig. 2C) in the cerebellum (–41%), ventral midbrain (–29%), and striatum (–25%) compared to respective controls. CAT activity was not significantly modified in the cortex, but showed a significant increase in the hippocampus (+35%). Effects of aluminium administration on the degeneration of DA terminals in the striatum In control rats, i.e. rats not lesioned with 6-OHDA (subgroup C) and rats treated with aluminium alone (subgroup D), the DAergic neurons in the pars compacta of the SN were intensely immunoreactive to TH, and a dense and evenly distributed TH immunoreactivity (TH-ir) was observed throughout the striatum, which indicated the presence of a dense network of nigrostriatal DAergic terminals (Fig. 3A-B). No significant changes in the density of DA striatal terminals were observed in control rats (i.e. not injected with 6-OHDA; subgroups C and D; Fig. 4). TH-ir terminal density was higher in the control groups (subgroups C and D; Fig. 3A-B) than in rats that were intraventricularly injected with 6-OHDA (subgroups E and F; Fig. 3C-D). We observed a significant decrease in TH-ir terminal density (–27%) in rats intraventricularly injected with 6-OHDA when compared to control rats (subgroup-C rats). In rats i.p. treated with aluminium and subjected to intraventricular injection of 6-OHDA (subgroup F), the reduction in the density of DA striatal terminals with respect to the control rats (subgroup D) and rats injected with 6-OHDA (subgroup E) was statistically significant (–48% and –28%, respectively; Fig. 4). 129
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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
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 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 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 160 and 161: CHAPTER 3 assume that the distinct
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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