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

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INTRODUCTION 2 PD, also called idiopathic PD or primary parkinsonism, is the most common movement disorder besides essential tremor and the second most common age-related neurodegenerative disease after Alzheimer's disease (AD) (Fahn and Przedborski 2000, Tanner and Aston 2000, Mayeux 2003, Fahn and Sulzer 2004). Moreover, PD is the main cause of chronic progressive Parkinsonism accounting for ~80% of cases. Parkinsonism, also known as Parkinson‟s syndrome, atypical Parkinson‟s or secondary Parkinson‟s, is a term which refers to the neurological syndrome characterised by three cardinal motor symptoms: bradykinesia, rigidity and tremor. Prevalence and incidence of PD More than 4.5 million people worldwide were affected by PD in 2007. Due to increasing life expectancy of the general population and multiplication of effective therapies, the number of individuals over 50 years of age with PD was expected to double to around 9 million patients in the world‟s 10 most populous nations between 2007 and the year 2030 (Dorsey et al. 2007). At the time of writing, PD is affecting approximately 6 million people worldwide. In regards to disease epidemiology, the mean age onset of sporadic PD (also known as idiopathic PD) is 55 years, but is now thought to be in the early-to-mid 60s (Inzelberg et al. 2002). Early onset of PD (EOPD) is rare, about 4% of patients develop clinical signs of the disease before 50 years (Van Den Eeden et al. 2003). Within EOPD, there appear to be two groups namely: young-onset PD (YOPD), with onset between 21 and 40 years, and juvenile Parkinsonism (JP), with onset at
INTRODUCTION PD is found in all ethnic groups, but with geographical differences in prevalence. Men seem to be slightly more prone to the disorder (Baldereschi et al. 2000, Lai et al. 2003, Benito-León et al. 2004). Incidence rates range from 8.6 to 19.0 per 100,000 inhabitants in the USA and Europe when strict diagnostic criteria of PD are applied (Twelves et al. 2003). Direct comparison of prevalence and incidence estimates are difficult and complicated because of methodological differences between studies (de Rijk et al. 1995, de Rijk et al. 1997b, Benito-León et al. 2003). Stricter diagnosis criteria, record-based studies or studies done in clinical settings yielded lower incidence or prevalence rates than door-to-door surveys or studies with in person examination (Schoenberg et al. 1988, Morgante et al. 1992, Tison et al. 1994, de Rijk et al. 1995, Claveria et al. 2002, Benito-León et al. 2003, Benito-León et al. 2004, de Lau et al. 2004). Clinical characteristics of PD PD exhibits great variability in clinical presentation as it presents with a range of motor, psychiatric, cognitive, sensory and autonomic symptoms. The three cardinal clinical symptoms of PD include rest tremor, rigidity, and bradykinesia. Often presented as “preclinical PD”, motor and non-motor features that may precede the cardinal motor symptoms by long periods of time should be taken more critically into consideration as they are part of the disease process (Figure 2; Langston 2006). Figure 2: The Parkinson’s complex (Langston 2006) 3
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: INTRODUCTION PARKINSON’S DISEASE
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 and 42: The death of SNpc DAergic neurons I
Page 43 and 44: INTRODUCTION the dorsomedial part o
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
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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
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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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REFERENCES
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