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

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INTRODUCTION Table 2: UK Parkinson’s Disease Society Brain Bank’s diagnostic criteria for the diagnosis of probable PD (Jankovic 2008, Davie 2008) Step 1: Diagnosis of a parkinsonian syndrome 10 Bradykinesia, and at least one of the following criteria: Muscular rigidity 4-6 Hz rest tremor Postural instability (not caused by primary visual, vestibular, cerebellar or propioceptive dysfunction) Step 2: Exclusion of other causes of parkinsonism i History of repeated strokes with stepwise progression of parkinsonian features ii History of repeated head injury iii History of definite encephalitis iv Oculogyric crises v Neuroleptic treatment at the onset of symptoms vi More than one affected relative vii Sustained remission viii Strictly unilateral features after 3 years ix Supranuclear gaze palsy x Cerebellar signs xi Early severe autonomic involvement xii Early severe dementia with disturbances of memory, language and praxis xiii Babinski’s sign xiv Presence of cerebral tumour or communicating hydrocephalus on CT scan xv Negative response to large doses of levodopa (if malabsorption excluded) Step 3: Supportive (prospective) criteria for PD (at least three or more required for diagnosis of definite PD) i Unilateral onset ii Rest tremor present iii Progressive disorder iv Persistent asymmetry affecting side of onset most v Excellent response (70–100%) to levodopa vi Severe levodopa-induced chorea (dyskinesia) vii Levodopa response for 5 years or more viii Clinical course of 10 years or more
INTRODUCTION Table 3: National Institute of Neurological Disorders (NINDS) diagnostic criteria for PD (Jankovic 2008) Group A features (characteristic of PD) Resting tremor Bradykinesia Rigidity Asymmetric onset Group B features (suggestive of alternative diagnoses) Features unusual early in the clinical course Prominent postural instability in the first 3 years after symptom onset Freezing phenomenon in the first 3 years Hallucinations unrelated to medications in the first 3 years Dementia preceding motor symptoms or in the first year Supranuclear gaze palsy (other than restriction of upward gaze) or slowing of vertical saccades Severe, symptomatic dysautonomia unrelated to medications Documentation of condition known to produce parkinsonism and plausibly connected to the patient’s symptoms (such as suitably located focal brain lesions or neuroleptic use within the past 6 months) Criteria for definite PD All criteria for probable Parkinson’s are met and Histopathological confirmation of the diagnosis is obtained at autopsy Criteria for probable PD At least three of the four features in group A are present and None of the features in group B is present (note: symptom duration >3 years is necessary to meet this requirement) and Substantial and sustained response to levodopa or a dopamine agonist has been documented Criteria for possible PD At least two of the four features in group A are present; at least one of these is tremor or bradykinesia and Either none of the features in group B is present or symptoms have been present (3 years and none of the features in group B is present and Either substantial and sustained response to levodopa or a dopamine agonist has been documented or the patient has not had an adequate trial of levodopa or a dopamine agonist 11
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: Table 1: Differential diagnostic in
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
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
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Excretion INTRODUCTION As insoluble
Page 87 and 88:
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
Page 114 and 115:
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
Page 204 and 205:
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REFERENCES Baquet Z. C., Bickford P
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REFERENCES 184 1,2,3,6-tetrahydropy
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Page 274:
REFERENCES Zhou W., Zhu M., Wilson
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