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

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INTRODUCTION Resting tremor 4 Resting tremor is the most commonly recognized feature of PD and the first motor symptom at disease onset in approximately 75% of PD patients (Jankovic et al. 1990, Hughes et al. 1993, Schrag et al. 2007). However, 25 % of patients with PD never develop tremor (Hughes et al. 1993). Rest tremor has a frequency of 4–6 Hz and classically resembles pill-rolling (descriptive of the rhythmic alternating motion of the forefinger and thumb). This motor manifestation/symptom is usually a supination- pronation tremor, asymmetric, and most prominent in the distal upper extremity as resting foot tremor is much less common than hand tremor as a presenting sign. Tremor at rest is lost during sleep and markedly decreased or abolished with voluntary movement (so typically it does not impair activities of daily living). It should be noted that PD tremor can also be seen to have a postural component. Nevertheless, rest tremor is worsened by excitement, anxiety, apprehension, contralateral motor activity, and is most easily seen when the patient is asked to ambulate with arms hanging at their sides. Observation of the patient during ambulation reveals much about the patient‟s symptoms, including rigidity and bradykinesia. Rigidity Rigidity is the raised resistance appreciated during the passive movement of the limb about a joint (often of a “lead pipe” quality). A “ratchety” sensation can be noted, indicating the contraction and relaxation of the muscles underlying the tremor. It can have a cogwheel quality even without tremor, but is usually more pronounced in the more tremulous limb. Rigidity is enhanced by contralateral motor activity or mental task performance. Bradykinesia and rigidity are less common then rest tremor but are still frequently seen at onset of PD.
Bradykinesia INTRODUCTION Bradykinesia, the most disabling symptom of PD, is easily observed. It results in the slowness in movement and as a consequence significantly impairs quality of life as everyday tasks performance is delayed (eating, dressing, arising from a chair, getting in and out of a car or bed). It initially manifests by difficulties with fine motor tasks (reduced arm swing in walking, speed of handwriting, doing up buttons) and often by decreased blink rate. Various tests can be performed to assess limb bradykinesia, such as fist closing and opening, finger and foot tapping, alternating forearm pronation and supination (Martinez-Martin et al. 1994). Additional motor symptoms are also noticeable as a result of hypokinesia (reduction in movement amplitude) and akinesia (absence of normal unconscious movements) in combination with rigidity, such as micrographia (decreased size of handwriting), reduced stride length in walking, hypophonia (diminished voice volume), dysarthia (slurred speech), hypomimia (facial masking of normal facial expression), and dysphagia (problems swallowing), and sialorrhea (drooling, failure to swallow without thinking about it). Postural instability Postural instability or the impairment of the righting reflex, sometimes judged a cardinal feature of PD, is non-specific and is less responsive to treatment compared with the others cardinal motor symptoms. Postural instability or gait disturbances refer to the gradual development of poor balance, leading to a high risk for falls and injuries, and sometimes, confinement to a wheelchair. It can be test with the retropulsion test (pulling the patient backward to check for balance recovery). This feature, in combination with rigidity and bradykinesia, results in important disability to the patient. Gait becomes slower, with shuffling, and turning is en bloc (as opposed to pivoting). Freezing is characterised by the inability to begin a voluntary movement such as walking or striking gait hesitation on turning or arriving at a real or perceived obstacle. Postural instability and gait abnormality are not typical at onset of PD. They are usually absent in early 5
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: INTRODUCTION PD is found in all eth
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
Page 77 and 78: 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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