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

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CHAPTER 2 RESULTS Aluminium distribution in the brain after oral and i.p. administration 110 As can be seen in Fig. 1, aluminium content in brain tissue was significantly increased in both aluminium-exposed groups (i.p. and oral) when compared to the corresponding control, except in VM of the i.p. aluminium-treated group. All brain regions of oral aluminium-treated animals showed significant increased levels of aluminium in relation to their controls: +69% CE, +200% VM, +116% CO, +66% H, +143% ST, with highest levels in the ventral midbrain>striatum>cortex, cerebellum and hippocampus. In orally-treated control animals, all areas showed a similar accumulation of aluminium. In i.p. aluminium-treated animals, aluminium content was significantly increased compared to the respective i.p. controls (+727% CE, +667% CO, +877% H and +294% ST). Notwithstanding, the level of aluminium in VM was significantly reduced compared to that of the control group (–83%). Aluminium in i.p. metal-treated animals seemed to accumulate preferentially in the following cerebral areas: hippocampus>cortex>striatum>cerebellum>ventral midbrain. When comparing the two different methods of aluminium administration, we noted a greater and significant increase of aluminium in the i.p. aluminium-treated groups compared to the orally-treated group: +77% H, +73% CO, +51% CE and +39% ST. In turn, aluminium concentration in VM was significantly reduced (–1963%).
DISCUSSION CHAPTER 2 Aluminium enters the brain through the BBB. Previous studies suggest that there are carrier-mediated mechanisms that allow uptake of aluminium into the brain and efflux into blood (Yokel 2002b). It was also proposed that aluminium distribution depends on the animal species in question and the chemical form of aluminium administered (Baydar et al. 2003). The aim of the present work was to evaluate the brain regional accumulation of aluminium in rats following the administration of aluminium chloride through two distinct administration routes: intraperitoneal and oral. Oral administration of aluminium chloride for four weeks resulted in a significant increase in brain aluminium concentration in all the investigated brain areas. These results agree with previous studies reporting an increase of aluminium concentration in both whole brain (Sahin et al. 1994) and specific areas of the brain (Gupta and Shukla 1995, Roig et al. 2006), which contribute to explain the impairment in motor coordination observed by some authors (Sahin et al. 1995). However, it has also been reported no significant accumulation of aluminium in the whole brain (Gómez et al. 1999, Colomina et al. 2002) and even a paradoxical reduction of aluminium concentration in the whole brain of mice chronically treated with a diet containing aluminium (Golub et al. 2000). This wide variety of results could be related with the aluminium salt used and/or the extent of brain area selected. Our results show that i.p aluminium chloride exposure for one week also caused a significant and greater aluminium accumulation in cerebellum, cortex, hippocampus and striatum, a finding that is consistent with previous literature concerning particular brain areas (Julka and Gill 1996a, Nayak and Chatterjee 2003, Abubakar et al. 2004b, Sakamoto et al. 2004). However, most of these publications used extensive cerebral regions. It has been also reported a no significant aluminium accumulation following i.p. administration of aluminium chloride (Moumen et al. 2001). The observation that i.p. administration of aluminium predominantly accumulates in the hippocampus is in accordance with a previous work (Julka and Gill 1996a). Our present study make the interesting point that, while oral administration of aluminium chloride resulted in a 111
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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
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 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: CHAPTER 2 atomization used were 1,5
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 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
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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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