Parkinsonian syndrome is an umbrella term including several diseases with similar symptoms. PET images are key when differential diagnosing patients with parkinsonsian syndrome. In this work two automatic diagnosing models are developed and evaluated, with PET images as input, and a diagnosis as output. The two devoloped models are evaluated based on performance, in terms of sensitivity, specificity and misclassification error. The models consists of 1) regression model and 2) either a decision tree or a random forest. Two coefficients, alpha and beta, are introduced to train and test the models. The coefficients are the output from the regression model. They are calculated with multiple linear regression, with the patient images as dependent variables, and mean images of four patient groups as explanatory variables. The coefficients are the underlying relationship between the two. The four patient groups consisted of 18 healthy controls, 21 patients with Parkinson's disease, 17 patients with dementia with Lewi bodies and 15 patients with vascular parkinsonism. The models predict the patients with misclassification errors of 27% for the decision tree and 34% for the random forest. The patient group which is easiest to classify according to both models is healthy controls. The patient group which is hardest to classify is vascular parkinsonism. These results implies that alpha and beta are interesting outcomes from PET scans, and could, after further development of the model, be used as a guide when diagnosing in the models developed.

A doença de Parkinson (DP) caracteriza-se por alterações deletérias no controle motor e, comumente, também produz prejuízos na regulação autonômica e função cardiovascular. O treinamento resistido traz benefícios motores para estes indivíduos, mas seus efeitos autonômicos e cardiovasculares ainda são desconhecidos. Assim, esta tese avaliou os efeitos do treinamento resistido sobre a regulação autonômica e a função cardiovascular de indivíduos com DP, comparando-os a indivíduos sem DP. Para tanto, 17 indivíduos sem DP (SDP, 67±10 anos) e 27 com DP (65±8 anos, estágios II-III da escala de Hoehn e Yahr modificado, estado \"on\" da medicação) foram estudados. Os indivíduos sem DP foram avaliados uma única vez e os com DP foram divididos aleatoriamente em dois grupos, grupo controle (DPCO: n=12) e treinamento resistido (DPTR: n=15 - 2 sessões/semana, 5 exercícios, 2-4 séries, 12-6 RM), e foram avaliados no início e no final das 12 semanas do estudo. No início do estudo, os indivíduos com DP apresentaram menor modulação parassimpática e maior modulação simpática e balanço simpatovagal cardíacos em repouso, além de pior resposta cardiovascular ao teste de se levantar e à manobra de Valsalva que os indivíduos sem DP. Ademais, apresentaram maior pressão arterial na posição deitada, maior débito cardíaco e menor resistência vascular periférica na posição sentada, menor descenso noturno da pressão arterial sistólica, maior frequência cardíaca de 24 horas e sono, e respostas cardiovasculares atenuadas ao exercício máximo. O treinamento resistido, no grupo DPTR, aumentou a força dinâmica máxima (88±23 vs. 108±27 kg, P < 0,05) e diminuiu a modulação simpática cardíaca (banda de baixa frequência da variabilidade da frequência cardíaca - deitado: 61±17 vs. 47±20 un; sentado: 60±11 vs. 46±15 un, P < 0,05) e a queda da pressão arterial sistólica ao teste de se levantar (-14±11 vs. -6±10 mmHg, P < 0,05), enquanto que nenhuma alteração foi observada no grupo DPCO. Nos demais parâmetros avaliados, não houve nenhum efeito do treinamento nos indivíduos com DP. Após as 12 semanas de estudo, o grupo DPTR apresentou modulação simpática cardíaca de repouso e resposta da pressão arterial sistólica ao teste de se levantar semelhantes aos indivíduos SDP e menores que o grupo DPCO (banda de baixa frequência da variabilidade da frequência cardíaca - deitado: 47±20 e 45±9 vs. 63±10 un e sentado: 46±15 e 49±10 vs. 61±13 un; redução da pressão arterial sistólica - 6±10 e -1±10 vs. -11±9 mmHg, respectivamente, P < 0,05). Em conclusão, em indivíduos com DP, o treinamento resistido diminuiu a modulação autonômica simpática cardíaca em repouso e a redução da pressão arterial sistólica ao teste de se levantar, igualando estas respostas às de indivíduos sem DP / Parkinson\'s disease (PD) is characterized by deleterious alterations in motor control, and it usually also presents with impairments on cardiovascular autonomic regulation and function. Resistance training promotes motor benefits in individuals with PD, but its autonomic and cardiovascular effects are still unknown. Thus, this thesis evaluated the effects of resistance training on cardiovascular autonomic regulation and function in subjects with PD, comparing them with subjects without PD. Seventeen subjects without PD (WPD, 67±10 years) and 27 with PD (65±8 years, stages II-III of modified Hoehn & Yahr scale, \"on\" state of medication) were studied. The subjects without PD were evaluated only once, while the subjects with PD were randomly divided into two groups, control (PDCO: n=12) and resistance training (PDRT: n=15 - 2 sessions/week, 5 exercises, 12-6 RM), and were evaluated at the beginning and after 12 weeks of study. At the beginning of the study, the subjects with PD presented, at rest, lower cardiac parasympathetic modulation and higher cardiac sympathetic modulation and sympathovagal balance as well as worse cardiovascular response to standing test and Valsalva Manoeuvre than individuals without PD. In addition, they had higher supine blood pressure, higher seated cardiac output, lower seated peripheral vascular resistance, lower nocturnal systolic blood pressure fall, higher 24 hours and nighttime heart rate and blunted cardiovascular responses to maximal exercise. Resistance training in the PDRT group increased maximal dynamic strength (88±23 vs. 108±27 kg, P < 0.05), decreased cardiac sympathetic modulation (low component of heart rate variability - supine: 61 ± 17 vs. 47 ± 20 nu and seated: 60 ± 11 vs. 46 ± 15 nu, P < 0.05) and systolic blood pressure decrease to standing test (-14±11 vs. -6±10 mmHg, P < 0.05), while no changes were observed in PDCO group. In the other parameters, there was no effect of training in the subjects with PD. After 12 weeks of the study, the PDRT group presented rest cardiac sympathetic modulation and systolic blood pressure response to standing test similar to WPD and lower than PDCO (low component of heart rate variability - supine: 47±20 and 45±9 vs. 63±10 nu and seated: 46±15 and 49±10 vs. 61±13 nu; systolic blood pressure reduction - -6±10 and -1±10 vs. -11±9 mmHg, respectively, P < 0.05). In conclusion, in individuals with PD, resistance training decreased rest cardiac sympathetic autonomic modulation and systolic blood pressure decrease to standing test, matching these responses to the ones observed in subjects without PD

A doença de Parkinson é uma patologia neurodegenerativa progressiva, que acomete mais de 1% da população acima de 60 anos, caracterizada pela morte de neurônios dopaminérgicos do sistema nigroestriatal. O tratamento atualmente disponível não fornece a cura para a doença de Parkinson. Contudo, a abordagem interdisciplinar tem sido capaz de melhorar a qualidade de vida dos indivíduos acometidos. Dados descrevem a relação entre o hábito de fumar e menor predisposição a esta doença, sugerindo que a nicotina proteja neurônios dopaminérgicos. Na área experimental, a prática de exercícios físicos também exerce efeitos benéficos nos modelos de parkinsonismo. Juntas, estas observações poderiam propor que a nicotina e o exercício físico atuariam sinergisticamente, de maneira a preservar os neurônios dopaminérgicos. Cinco grupos de ratos Wistar foram submetidos ao implante de pastilhas de nicotina ou placebo e dois destes grupos foram colocados em gaiolas-moradia com acesso às rodas de correr, durante duas semanas. Os outros grupos permaneceram em gaiolas-moradia simples. Foi realizada lesão estriatal unilateral com 6-OHDA em quatro grupos, após a qual os ratos permaneceram em suas respectivas gaiolas, por outras 5 semanas. Os animais foram submetidos por três vezes a testes comportamentais, ao longo das 7 semanas. Por fim, as áreas de interesse foram removidas e processadas para as técnicas de Western Blotting e PCR em tempo real. Os ratos submetidos à atividade física espontânea, com ou sem nicotina, não mostraram déficit na pata contralateral à lesão, contrastando com os ratos sedentários. A interação nicotina - atividade física mostrou-se importante para que a síntese de TH e de NF-200 não diminuísse, além de aumentar os níveis de RNAm do BDNF no corpo estriado e mesencéfalo ventral ipsilaterais à lesão. Estes resultados sugerem que a nicotina sistêmica, associada à atividade física, podem induzir alterações nos núcleos da base, que facilitariam a neuroproteção dos terminais dopaminérgicos estriatais. / Parkinsons disease is a progressive neurodegenerative pathology that affects 1% of the elderly population characterized by death of dopaminergic neurons at the nigrostriatal system. Nowadays the cure is not possible with the treatments available, but an interdisciplinary approach improves the quality of life. It has been already described a relationship between smoking habit and less predisposition for this pathology, suggesting that nicotine could be able to protect dopamine neurons. Besides, it is known that physical activity offers benefic effects in Parkinsons disease models. Together, these observations suggest that nicotine and exercise can act synergistically for dopaminergic neurons protection. Five groups of Wistar rats underwent an operation to implant a nicotine or placebo pellet; two rats were placed in cages with running wheels for 2 weeks after surgery. Remaining groups were maintained in simple cages. Four groups received striatal injection with 6-OHDA, and were returned to their respective cages for additional 5 weeks. Rats were submitted 3 times to behavioral tests along these 7 weeks. At the end of this period, brain areas of interest were removed and submitted to immunoblotting and real-time RT-PCR. Rats exposed to running wheels (placebo and nicotine groups) did not show deficit in the contralateral paw, contrasting to the findings of parkinsonism without physical activity. Nicotine and exercise counteracted the striatal down-regulation of TH synthesis and NF-200 levels. Combined strategies also increased BDNF mRNA levels in the ipsilateral striatum and ventral mesencephalon. Systemic nicotine associated to physical exercise may trigger trophic events in basal ganglia that could lead to neuroprotection within striatal dopaminergic terminals.

Background: Single photon emission computed tomography (SPECT) with dopamine transporter (DAT) and dopamine D2 receptor (D2R) ligands can visualise the integrity of the nigrostriatal dopamine system. Parkinson’s disease (PD) and the atypical parkinsonian diseases (APD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), have similar symptoms and dopamine depletion, but differ in pharmacological response and prognosis. Clinical differentiation between PD and APD is often difficult in the early stages. The aims of the thesis were to evaluate the differential diagnostic and prognostic value of SPECT in early PD, MSA and PSP, to map the pattern of progression with dopamine SPECT, and map the pattern of dopamine SPECT in non-affected elderly volunteers with a prospective approach. Also, we evaluated the methodological aspects of dopamine SPECT with respect to image evaluation tools, reconstruction parameters and gamma cameras. Methods: 172 patients, included in an on-going clinical prospective study on idiopathic parkinsonism, participated in the SPECT study. Also, 31 age-matched healthy controls (HC) were followed within this study. SPECT was done with 123I-FP-Cit (DAT SPECT) and 123I-IBZM (D2R SPECT). Regions of interest (ROI) were used as a standard method for semi-quantitative image analysis. Results: SPECT uptake ratios from different gamma cameras could be equalised through correction equations derived from images of a brain-like phantom, provided that attenuation correction was applied. The ROI method had high reproducibility. SPECT uptake  in HC, measured with the ROI method and a volume based (VOI) method rendered similar trends, but gender and age differences in SPECT uptake were more marked with the VOI method, and less pronounced in DAT SPECT compared to D2R SPECT with both methods. The DAT SPECT uptake was significantly reduced in very early disease stage of PD and APD compared to HC. DATSPECT uptake was more reduced in PD with postural and gait disturbance (PIGD) compared to tremor-dominant PD. Decline in DAT SPECT uptake during the first year was more pronounced in PD and PSP compared to HC. D2R SPECT uptake overlapped between untreated PD and APD. After initiated treatment, the D2R SPECT uptake was significantly higher in MSA patients compared to PD, PSP and HC. Decline in D2R SPECT uptake during the first year was not significantly different between patients or compared to HC. Conclusions: 123I-FP-Cit SPECT is a valuable and sensitive method to detect early stage idiopathic parkinsonism. A different level of uptake between PIGD-PD compared to TD-PD indicates a prognostic potential. It is not possible to differ between PD, MSA and PSP in early stage with 123I-FP-Cit SPECT and no differential diagnostic value was found using 123I-IBZM SPECT in the early, untreated stage of PD, MSA and PSP. A different pattern of uptake of this ligand in MSA compared to PD and PSP during the first years of L-dopa treatment may, however, indicate a diagnostic value during the follow-up period.

A doença de Parkinson (DP) caracteriza-se por alterações deletérias no controle motor e, comumente, também produz prejuízos na regulação autonômica e função cardiovascular. O treinamento resistido traz benefícios motores para estes indivíduos, mas seus efeitos autonômicos e cardiovasculares ainda são desconhecidos. Assim, esta tese avaliou os efeitos do treinamento resistido sobre a regulação autonômica e a função cardiovascular de indivíduos com DP, comparando-os a indivíduos sem DP. Para tanto, 17 indivíduos sem DP (SDP, 67±10 anos) e 27 com DP (65±8 anos, estágios II-III da escala de Hoehn e Yahr modificado, estado \"on\" da medicação) foram estudados. Os indivíduos sem DP foram avaliados uma única vez e os com DP foram divididos aleatoriamente em dois grupos, grupo controle (DPCO: n=12) e treinamento resistido (DPTR: n=15 - 2 sessões/semana, 5 exercícios, 2-4 séries, 12-6 RM), e foram avaliados no início e no final das 12 semanas do estudo. No início do estudo, os indivíduos com DP apresentaram menor modulação parassimpática e maior modulação simpática e balanço simpatovagal cardíacos em repouso, além de pior resposta cardiovascular ao teste de se levantar e à manobra de Valsalva que os indivíduos sem DP. Ademais, apresentaram maior pressão arterial na posição deitada, maior débito cardíaco e menor resistência vascular periférica na posição sentada, menor descenso noturno da pressão arterial sistólica, maior frequência cardíaca de 24 horas e sono, e respostas cardiovasculares atenuadas ao exercício máximo. O treinamento resistido, no grupo DPTR, aumentou a força dinâmica máxima (88±23 vs. 108±27 kg, P < 0,05) e diminuiu a modulação simpática cardíaca (banda de baixa frequência da variabilidade da frequência cardíaca - deitado: 61±17 vs. 47±20 un; sentado: 60±11 vs. 46±15 un, P < 0,05) e a queda da pressão arterial sistólica ao teste de se levantar (-14±11 vs. -6±10 mmHg, P < 0,05), enquanto que nenhuma alteração foi observada no grupo DPCO. Nos demais parâmetros avaliados, não houve nenhum efeito do treinamento nos indivíduos com DP. Após as 12 semanas de estudo, o grupo DPTR apresentou modulação simpática cardíaca de repouso e resposta da pressão arterial sistólica ao teste de se levantar semelhantes aos indivíduos SDP e menores que o grupo DPCO (banda de baixa frequência da variabilidade da frequência cardíaca - deitado: 47±20 e 45±9 vs. 63±10 un e sentado: 46±15 e 49±10 vs. 61±13 un; redução da pressão arterial sistólica - 6±10 e -1±10 vs. -11±9 mmHg, respectivamente, P < 0,05). Em conclusão, em indivíduos com DP, o treinamento resistido diminuiu a modulação autonômica simpática cardíaca em repouso e a redução da pressão arterial sistólica ao teste de se levantar, igualando estas respostas às de indivíduos sem DP / Parkinson\'s disease (PD) is characterized by deleterious alterations in motor control, and it usually also presents with impairments on cardiovascular autonomic regulation and function. Resistance training promotes motor benefits in individuals with PD, but its autonomic and cardiovascular effects are still unknown. Thus, this thesis evaluated the effects of resistance training on cardiovascular autonomic regulation and function in subjects with PD, comparing them with subjects without PD. Seventeen subjects without PD (WPD, 67±10 years) and 27 with PD (65±8 years, stages II-III of modified Hoehn & Yahr scale, \"on\" state of medication) were studied. The subjects without PD were evaluated only once, while the subjects with PD were randomly divided into two groups, control (PDCO: n=12) and resistance training (PDRT: n=15 - 2 sessions/week, 5 exercises, 12-6 RM), and were evaluated at the beginning and after 12 weeks of study. At the beginning of the study, the subjects with PD presented, at rest, lower cardiac parasympathetic modulation and higher cardiac sympathetic modulation and sympathovagal balance as well as worse cardiovascular response to standing test and Valsalva Manoeuvre than individuals without PD. In addition, they had higher supine blood pressure, higher seated cardiac output, lower seated peripheral vascular resistance, lower nocturnal systolic blood pressure fall, higher 24 hours and nighttime heart rate and blunted cardiovascular responses to maximal exercise. Resistance training in the PDRT group increased maximal dynamic strength (88±23 vs. 108±27 kg, P < 0.05), decreased cardiac sympathetic modulation (low component of heart rate variability - supine: 61 ± 17 vs. 47 ± 20 nu and seated: 60 ± 11 vs. 46 ± 15 nu, P < 0.05) and systolic blood pressure decrease to standing test (-14±11 vs. -6±10 mmHg, P < 0.05), while no changes were observed in PDCO group. In the other parameters, there was no effect of training in the subjects with PD. After 12 weeks of the study, the PDRT group presented rest cardiac sympathetic modulation and systolic blood pressure response to standing test similar to WPD and lower than PDCO (low component of heart rate variability - supine: 47±20 and 45±9 vs. 63±10 nu and seated: 46±15 and 49±10 vs. 61±13 nu; systolic blood pressure reduction - -6±10 and -1±10 vs. -11±9 mmHg, respectively, P < 0.05). In conclusion, in individuals with PD, resistance training decreased rest cardiac sympathetic autonomic modulation and systolic blood pressure decrease to standing test, matching these responses to the ones observed in subjects without PD

A doença de Parkinson é uma patologia neurodegenerativa progressiva, que acomete mais de 1% da população acima de 60 anos, caracterizada pela morte de neurônios dopaminérgicos do sistema nigroestriatal. O tratamento atualmente disponível não fornece a cura para a doença de Parkinson. Contudo, a abordagem interdisciplinar tem sido capaz de melhorar a qualidade de vida dos indivíduos acometidos. Dados descrevem a relação entre o hábito de fumar e menor predisposição a esta doença, sugerindo que a nicotina proteja neurônios dopaminérgicos. Na área experimental, a prática de exercícios físicos também exerce efeitos benéficos nos modelos de parkinsonismo. Juntas, estas observações poderiam propor que a nicotina e o exercício físico atuariam sinergisticamente, de maneira a preservar os neurônios dopaminérgicos. Cinco grupos de ratos Wistar foram submetidos ao implante de pastilhas de nicotina ou placebo e dois destes grupos foram colocados em gaiolas-moradia com acesso às rodas de correr, durante duas semanas. Os outros grupos permaneceram em gaiolas-moradia simples. Foi realizada lesão estriatal unilateral com 6-OHDA em quatro grupos, após a qual os ratos permaneceram em suas respectivas gaiolas, por outras 5 semanas. Os animais foram submetidos por três vezes a testes comportamentais, ao longo das 7 semanas. Por fim, as áreas de interesse foram removidas e processadas para as técnicas de Western Blotting e PCR em tempo real. Os ratos submetidos à atividade física espontânea, com ou sem nicotina, não mostraram déficit na pata contralateral à lesão, contrastando com os ratos sedentários. A interação nicotina - atividade física mostrou-se importante para que a síntese de TH e de NF-200 não diminuísse, além de aumentar os níveis de RNAm do BDNF no corpo estriado e mesencéfalo ventral ipsilaterais à lesão. Estes resultados sugerem que a nicotina sistêmica, associada à atividade física, podem induzir alterações nos núcleos da base, que facilitariam a neuroproteção dos terminais dopaminérgicos estriatais. / Parkinsons disease is a progressive neurodegenerative pathology that affects 1% of the elderly population characterized by death of dopaminergic neurons at the nigrostriatal system. Nowadays the cure is not possible with the treatments available, but an interdisciplinary approach improves the quality of life. It has been already described a relationship between smoking habit and less predisposition for this pathology, suggesting that nicotine could be able to protect dopamine neurons. Besides, it is known that physical activity offers benefic effects in Parkinsons disease models. Together, these observations suggest that nicotine and exercise can act synergistically for dopaminergic neurons protection. Five groups of Wistar rats underwent an operation to implant a nicotine or placebo pellet; two rats were placed in cages with running wheels for 2 weeks after surgery. Remaining groups were maintained in simple cages. Four groups received striatal injection with 6-OHDA, and were returned to their respective cages for additional 5 weeks. Rats were submitted 3 times to behavioral tests along these 7 weeks. At the end of this period, brain areas of interest were removed and submitted to immunoblotting and real-time RT-PCR. Rats exposed to running wheels (placebo and nicotine groups) did not show deficit in the contralateral paw, contrasting to the findings of parkinsonism without physical activity. Nicotine and exercise counteracted the striatal down-regulation of TH synthesis and NF-200 levels. Combined strategies also increased BDNF mRNA levels in the ipsilateral striatum and ventral mesencephalon. Systemic nicotine associated to physical exercise may trigger trophic events in basal ganglia that could lead to neuroprotection within striatal dopaminergic terminals.

Objective: Vestibular Evoked Myogenic Potentials (VEMP) were investigated to differentiate between parkinsonian syndromes. We correlated balance and VEMP parameters to investigate the VEMP brainstem circuits as possible origin for postural instability. Methods: We assessed clinical status, ocular and cervical VEMP (oVEMP, cVEMP) and a balance assessment (posturography, Activities-specific Balance Confidence Scale, Berg Balance Scale, modified Barthel Index) in 76 subjects: 30 with Parkinson’s disease (PD), 16 with atypical parkinsonism (AP) and 30 healthy controls. VEMP were elicited by using a mini-shaker on the forehead. Results: Patients with PD had a prolonged oVEMP n10 in comparison to controls and prolonged p15 compared to controls and AP. Patients with AP showed reduced oVEMP amplitudes compared to PD and controls. CVEMP did not differ between groups. Postural impairment was higher in AP compared to controls and PD, particularly in the rating scales. No correlations between VEMP and posturography were found. A classifier using support vector machine was able to automatically classify controls and patient subgroups with moderate to good accuracy based on oVEMP latencies and balance questionnaires. Conclusions: Both oVEMP and posturography, but not cVEMP, may be differentially affected in PD and AP. We did not find evidence that impairment of the cVEMP or oVEMP pathways is directly related to postural impairment. Significance: OVEMP and balance assessment could be implemented in the differential diagnostic work-up of parkinsonian syndromes.:1. Einleitung 2. Publikationsmanuskript 3. Zusammenfassung 4. Literaturverzeichnis 5. Anlagen 6. Darstellung des eigenen Beitrages 7. Selbstständigkeitserklärung 8. Lebenslauf 9. Danksagung

No description available.

No description available.

The developing brain goes through a number of developmental periods during which it displays an increased sensitivity to exogenous disturbances. On such period is the so called “Brain growth spurt” (BGS) which in humans takes place starting from the third trimester of pregnancy and throughout the first few years of life. The corresponding period in rats and mice is the first postnatal weeks. Exposure to relatively modest concentrations of the brominated flame retardant PBDE-99 during the second week of life in mice causes a more or less permanent impairment in the ability of the animals to adjust properly to environmental changes at adulthood. This “late response on early exposure” reflects the long-term consequences of disrupting the developing brain during a sensitive time period. The cellular mechanisms underlying the behavioral effects are far from clear. To address the initial damage occurring around the time of exposure, the approach used in this thesis is to use proteomics to analyze the effects of PBDE-99 on protein expression soon (24 hours) after exposure of the neonatal mouse on postnatal day (PND) 10.The thesis comprises the effects on the proteome in three distinct brain parts: cerebral cortex, striatum and the hippocampus. In addition, an in vitro model was developed and used to evaluate the PBDE-99 effects on cultured cerebral cortex cells from embryonic rat brains. Gel-based proteomics (2D-DIGE) coupled to MALDI- or ESI-MS has been used throughout for the proteomics experiments, but other techniques aimed at analyzing both proteins and mRNA have also been used to better characterize the effects. Even if the protein complements expressed by the different brain parts and separated with 2D-DIGE are seemingly similar, the effects are apparently specific for the different brain regions. In hippocampus, PBDE induces effects on proteins involved in metabolism and energy production, while the effects in striatum point towards effects on neuroplasticity. PBDE-99 changes the expression of cytoskeletal proteins in the cerebral cortex 24 hours after exposure. Interestingly, in vitro exposure of cerebral cortex cells to a PBDE-99 concentration in the same order of magnitude as in the in vivo neonatal brain also induces cytoskeletal effects, in the absence of cytotoxicity. This may suggest effects on regulatory aspects of cytoskeletal dynamics such as those involved in neurite sprouting. This thesis also addresses the problems involved in presenting proteomics data. Many of the available methods and approaches for presenting transcriptomics data are not suitable for isoform rich protein data. Modifications of existing methods and the development of a new approach (DEPPS) is also presented. Most importantly, the thesis presents the application and usefulness of proteomics as hypothesis generating techniques in neurotoxicology.