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

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INTRODUCTION reduced activity in the “direct” pathway and increased activity in the “indirect” pathway, resulting in excessive GPi/SNpr inhibitory output to the thalamus (Figure 11). These changes lead to a hypokinetic disorder characterized by inhibition of movement (Kreitzer and Malenka 2008). Figure 10: Human brain sections immunostained for DAT of normal person (A) and PD patient (B) (Betarbet et al. 2002) 18 Neuroimaging and pathological studies suggest that there is a long latency between nigral degeneration begin and symptoms onset. The presymptomatic latent phase was estimated to be approximately 6 years in idiopathic PD and longer in familial PD (Fearnley et al. 1991, Morrish et al. 1996, Hilker et al. 2005). This long asymptomatic period indicates that compensatory mechanisms are able to deal with progressively lower DA levels in order to preserve apparent normal BG function. These compensatory mechanisms which comprise increased striatal DA turnover and receptor sensitivity, upregulation of striatopallidal enkephalin levels, increased subthalamic excitation of GPe, and maintenance of cortical motor area activation (Bezard et al. 1999, Bezard et al. 2001), might be potentially damaging to nigral neurons through rising cellular metabolic demand, oxidative stress, and excitotoxicity (Rodriguez et al. 1998, Jenner 2003). The PD-associated cell loss has a characteristic topology distinct from the pattern seen in the course of normal aging of the human organism as the SN is characterized by a low level of neuronal degeneration (Kubis et al. 1995). Furthermore, normal aging-related morphological modifications were found to be most intensive in
INTRODUCTION the dorsomedial part of SNpc while in PD the ventrolateral and caudal portions of SNpc are particularly affected (Fearnley and Lees 1991). Figure 11: Classical model of the BG in the normal state (A) and parkinsonian state (B) (Obeso et al. 2008) 19
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: The death of SNpc DAergic neurons I
Page 45 and 46: INTRODUCTION characterized as are l
Page 47 and 48: INTRODUCTION (Olanow et al. 2004).
Page 49 and 50: Etiology and pathogenesis of PD INT
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
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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
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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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