Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 5 uppsatser.

Thesis (Ph.D)--University of Adelaide, Dept. of Animal Sciences, 1991? / Includes bibliographical references (leaves 166-195).

Thesis (M.S. in Applied Science (Operations Research))--Naval Postgraduate School, June 2004. / Cover title. "June 2004." Thesis advisor: Nita Lewis Miller. Performed by Naval Postgraduate School, Monterey, CA. Includes bibliographical references (p. 103-107). Also available online from the Naval Postgraduate School (NPS), Dudley Knox Library site (http://www.nps.edu/Library/). Address as of 10/10/06: http://stinet.dtic.mil/cgi-bin/GetTRDoc?AD=ADA424687&Location=U2&doc=GetTRDoc.pdf. Also available in microfiche.

Os esteróides gonadais exercem importantes influências no direcionamento da resposta imune do hospedeiro frente à infecção. Alterações decorrentes de sua ausência ou reposição podem significar em uma evolução distinta de determinada parasitose. Existe também uma relação entre a produção de melatonina e o ritmo de atividade do sistema imune. A resposta imune depende de uma interação entre inúmeros hormônios que irão agir sinergicamente com distintas células imunes. O objetivo desse trabalho foi investigar o efeito dos hormônios sexuais masculinos, através da orquiectomia, e da administração oral de melatonina sobre a resposta imune de ratos Wistar machos infectados com a cepa Y de Trypanosoma cruzi, durante a fase aguda da doença de Chagas experimental. Inúmeros parâmetros foram avaliados, entre eles: parasitemia, histologia cardíaca, peso dos animais e órgãos, linfoproliferação de timócitos e esplenócitos, quantificação de macrófagos, dosagem de óxido nítrico, citometria de fluxo para avaliação das populações de CD3+CD4+ e CD3+CD8+; e ensaios imunológicos como IFN-gama, IL-2, IL-6, IL-12, IL-10. Observou-se em todos os parâmetros analisados a ação sinérgica da melatonina e da orquiectomia sobre o sistema imune, favorecendo uma resposta positiva contra o parasita na fase aguda da infecção. Dessa forma, concluiu-se que a melatonina e a redução dos hormônios sexuais masculinos exerceram um papel imunoestimulador importante, que se refletiu em uma resposta mais efetiva do hospedeiro durante a infecção experimental. / Gonadal steroids exert important influence in the host immune response during infection. Changes resulting from the absence or replacement of these hormones may represent a distinct evolution of a particular parasite. There is also a relationship between melatonin production and the rhythmic activity of the immune system. The immune response depends on the interaction of many hormones that will act synergistically with other immune cells. The objective of this research was to evaluate the effect of male sex hormones through orchiectomy, and oral administration of melatonin on the immune response of male Wistar rats infected with the Y strain of Trypanosoma cruzi, during the acute phase of experimental Chagasdisease. Several parameters were evaluated among them: quantification of blood parasites, heart histology, body weight of animals and organs, lymphoproliferation of thymocytes and splenocytes, quantification of peritoneal macrophages, nitric oxide concentration, alterations in CD3+CD4+ and CD3+CD8+ lymphocyte populations by flow cytometry and immunological assays, as IFN-gama, IL-2, IL-6, IL-12, IL-10. It was observed in all parameters examined the synergistic action of melatonin and orchiectomy on the immune system, promoting a positive response against the parasite in the acute phase of infection. Thus, it was concluded that melatonin and the absence of male sex hormones exerted an important immunostimulating role, which reflected a more effective hosts response during the experimental infection.

O sistema imune do hospedeiro acometido pela doença de Chagas tem sido alvo de importantes pesquisas que podem favorecer avanços no entendimento dos mecanismos patogênicos relacionados à doença. No presente estudo, investigamos possíveis ações benéficas provenientes de efeitos anti-inflamatórios e antioxidantes da associação terapêutica (melatonina/meloxicam) sobre a cardiomiopatia chagásica crônica. Foram analisadas citocinas e outros mediadores envolvidos no processo inflamatório característico da infecção. Além disso, níveis plasmáticos de Creatina Fosfoquinase MB (CK-MB), número de focos inflamatórios no tecido cardíaco e análise do peso relativo do coração foram avaliados como fatores preditivos da redução dos danos no miocárdio após os diferentes tratamentos. Como modelo experimental, foram utilizados ratos wistar infectados pela cepa Y de T. cruzi e tratados ou não com melatonina, meloxicam, ou associação de ambos. As células inflamatórias e o parasitismo tecidual cardíaco foram avaliados por meio de técnica histológica. A técnica ELISA foi utilizada para detecção e quantificação de citocinas pró-inflamatórias e modulatórias no miocárdio e nos soros dos animais experimentais. Também foram investigados os níveis de nitrito produzidos por macrófagos e por células cardíacas dos grupos experimentais pela reação de Griess. Os parâmetros foram investigados durante a fase: crônica (90, 120 e 180) dias após a infecção. O estudo poderá contribuir para um melhor entendimento das respostas imunológicas anti-T. cruzi, bem como da patogenia da disfunção cardíaca chagásica crônica. / The host immune system affected by Chagas disease has been the subject of important research that can promote advances in the understanding the pathogenic mechanisms related to the disease. In the present study, it was investigated the possible beneficial actions of the anti-inflammatory and antioxidant combination therapy (melatonin / meloxicam) on chronic Chagas cardiomyopathy. Some cytokines and other mediators involved in the inflammatory process characteristic of infection were analyzed. In addition, plasma levels of creatine phosphokinase MB (CK-MB), number of inflammatory foci in the cardiac tissue and analysis of the relative weight of the heart were evaluated as predictors of damage reduction in the myocardium after different treatments. As experimental model, we used Wistar rats infected with the Y strain of T. cruzi. Some groups were untreated and others treated with melatonin, meloxicam, or combination of both. Inflammatory cells and heart tissue parasitism were evaluated by histological technique. Some pro-inflammatory and modulatory cytokines were quantified by ELISA technique in the myocardium and serum from experimental animals. The production of nitrite by macrophages and cardiac cells of the experimental groups was also investigated through Griess reaction. The parameters were observed during the chronic stage: (90, 120, and 180) days after infection. The study may contribute to a better understanding of the anti-T. cruzi immunological responses, as well as the pathogenesis of chronic Chagas heart dysfunction.

Submitted by GABRIELA MELLONI ZUCULO null (gabriela.zuculo@gmail.com) on 2016-05-11T20:23:14Z No. of bitstreams: 1 DISSERTAÇÃO DEFESA GABRIELA ZUCULO PRONTO.pdf: 2423369 bytes, checksum: 1518ae3189c9a9ce35d3608fa0a5a980 (MD5) / Approved for entry into archive by Felipe Augusto Arakaki (arakaki@reitoria.unesp.br) on 2016-05-13T16:28:45Z (GMT) No. of bitstreams: 1 zuculo_gm_me_mar.pdf: 2423369 bytes, checksum: 1518ae3189c9a9ce35d3608fa0a5a980 (MD5) / Made available in DSpace on 2016-05-13T16:28:45Z (GMT). No. of bitstreams: 1 zuculo_gm_me_mar.pdf: 2423369 bytes, checksum: 1518ae3189c9a9ce35d3608fa0a5a980 (MD5) Previous issue date: 2016-04-19 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / As características comuns ao quadro do Transtorno do Espectro do Autismo (TEA) destacadas pelo DSM-5 são: déficit de comunicação, dificuldade em fazer amizades ou se relacionar, dependência de rotina, resistência a mudanças e obsessão por itens inapropriados. Tais comportamentos podem ser observados desde a infância, porém com variações em cada indivíduo, o que levou o TEA a ser considerado um “continuum” que varia de menos comprometido (leve) a muito comprometido (grave). Dentre a complexa sintomatologia do TEA nos diferentes graus destaca-se a alta prevalência de distúrbios de sono, com influência negativa nas alterações comportamentais, instabilidade de humor, déficits nas funções neurocognitivas, incluindo memória, atenção, criatividade verbal, flexibilidade cognitiva e raciocínio abstrato. Como possível causa dos distúrbios de sono nessa população, está o déficit na produção de melatonina, hormônio que tem dentre suas funções a modulação da qualidade do sono. Com o intuito de fornecer dados para futuros tratamentos visando à melhora da qualidade de vida de indivíduos com TEA, esse estudo teve como objetivo investigar parâmetros de ritmo sono-vigília, aspectos comportamentais e de fluência verbal, antes e após o uso de melatonina exógena em indivíduos com TEA leve. Indivíduos com TEA leve de ambos os gêneros, de 7 a 18 anos, foram avaliados por meio da Escala de sono para crianças (EDSC), actigrafia, Child Behavior Checklist (CBCL) e Teste de fluência verbal fonêmica antes e após o uso oral de melatonina (3mg). A análise estatística descritiva foi feita a partir da média e erro padrão da média ou do percentual nos diferentes parâmetros e a análise estatística inferencial foi feita a partir do teste Anova com o teste de Tukey (pós-teste) e o teste de correlação de Spearman. Os resultados mostraram que 55,5% dos participantes com TEA leve apresentam indicativo de ao menos um distúrbio de sono, sendo os maiores percentuais encontrados em distúrbios de hiperidrose de sono, distúrbios respiratórios de sono e distúrbios de início e manutenção de sono. O grupo que recebeu melatonina apresentou os menores percentuais de distúrbios de sono com exceção do distúrbio de hiperidrose do sono. A análise da actigrafia mostrou que: o grupo TEA leve melatonina apresentou maior tempo total de sono em comparação aos outros grupos. Houve divergência sobre o ritmo atividade-repouso entre os parâmetros de fragmentação e amplitude do ritmo, sendo encontrado que o grupo TEA leve melatonina apresentou: ritmo menos fragmentado segundo o Aczcm e o IVm; e maior amplitude de ritmo segundo RAd e menor amplitude de ritmo segundo Sumpim. Os resultados do inventário de comportamento indicaram que as crianças com TEA leve apresentam os maiores escores classificados como clínico em problemas de pensamento, ansiedade, retraimento, comportamentos internalizantes e comportamentos externalizantes. O grupo que recebeu melatonina apresentou menores percentuais de escores classificados como clínico pelo inventário CBCL. A média de acertos no teste de fluência verbal fonêmica no grupo TEA leve foi de 13,9 ± 1,6. Quando separado por letras, o resultado foi P= 5,4 ± 0,7, T= 4,3 ± 0,5, L= 4,6 ± 0,6. Houve correlação entre os distúrbios totais de sono e os problemas somáticos de comportamento apresentados pelo grupo TEA leve. Estes dados mostram que crianças com TEA leve apresentam alta incidência de distúrbios de sono assim como no TEA sem especificação de grau, porém em menor escala. Estes distúrbios afetam aspectos comportamentais destas crianças e o tratamento com melatonina pode levar a melhora deste quadro. A fluência verbal de crianças com TEA grau leve é similar a de crianças com desenvolvimento típico. / The features common to the ASD highlighted by the DSM-5 are: communication deficit, difficulty making friends or relating, routine dependence, resistance to change, inappropriate items obsession. Such behavior can be verified since childhood, but with individual variations, which led the ASD to be considered as a "continuum" ranging from less committed (mild) to very committed (serious). Among the complex symptoms of ASD there is the high prevalence of sleep disorders, with a negative influence on behavioral changes, mood instability, deficits in neurocognitive functions including memory, attention, verbal creativity, cognitive flexibility and abstract reasoning. As a possible cause of sleep disorders in this population is the deficit of the melatonin production, hormone that modulates the sleep quality. In order to collaborate with future treatments that improving the life quality of ASD individuals, this study aimed to investigate parameters of sleep wake rhythm, behavior and verbal fluency before and after exogenous melatonin use in mild ASD individuals. For this, mild ASD individuals of both genders, 7-18 years were assessed by Sleep Disturbance Scale for Children (SDSC), actigraphy, Child Behavior Checklist (CBCL) and phonemic verbal fluency test before and after oral melatonin (3 mg). Descriptive statistical analysis was analyzed by mean and standard error or by percentage of the different parameters and inferential statistical analysis was performed by ANOVA with Tukey test (post-test) and Spearman correlation test. The results showed that 55,5% of mild ASD participants showed at least one sleep disorder, with the highest percentages found in sleep hyperhidrosis, sleep-breathing disorders and disorders of initiating and maintaining sleep. The group receiving melatonin had the lowest percentage of sleep disorders with the exception of sleep hyperhidrosis disorder. The actigraphy showed that: the mild ASD melatonin group showed higher total time of sleep than other groups. There was disagreement about between fragmentation parameters and amplitude of the activity-rest rhythm, since was found that the group of mild ASD melatonin showed: less fragmented rhythm according to Aczcm and IVm; and greater amplitude following Rad and lower amplitude rhythm following Sumpim. The results of behavior indicated that children with mild ASD have the high scores classified as clinical problems in thinking, anxiety, withdrawal, internalizing behaviors and externalizing behaviors. The group receiving melatonin had lower percentages of scores classified as clinical CBCL inventory. The mean score on the verbal fluency test in the group of mild ASD was 13,9 ± 1,6. When separated by letter, the result was P= 5,4 ± 0,7, T= 4,3 ± 0,5, L= 4,6 ± 0,6. There was a correlation between total sleep disorders and somatic behavior problems presented by mild ASD group. These data show that children with mild ASD have a high incidence of sleep disorders as well as in the ASD level without specification, but to a lesser extent. These disorders affect behavioral aspects of these children and the treatment with melatonin can improve of the clinical condition. Verbal fluency of children with ASD mild is similar to typically developing children.

Psychotic-like experiences (PLEs) are prevalent occurrences deemed comparable with the symptoms of psychosis, but not sufficiently severe to warrant a diagnosis upon clinical presentation. Their presence is associated with several adverse clinical outcomes: the onset of various common mental health disorders (e.g. anxiety, mood, substance abuse), poorer functioning, non-remission and relapse. Sleep and circadian rhythm disruption (SCRD) is observed in 30-80% of patients with psychosis. The omnipotence of SCRD across all phases of the disorder (including the prodromal, acute, chronic and residual phases) raises the question as to whether SCRD may directly contribute to the development of psychosis. Assuming that PLEs are along the same continuum to developing psychosis, a logical next step to further disentangle the sleep-psychosis relationship is to examine whether SCRD relates to the experience of PLEs and whether this relationship is bi-directional. This thesis begins by examining the core predictions made by a continuum model of understanding psychosis and how specific parameters of sleep may influence PLEs. A smaller high-definition cross-sectional study follows, examining biological underpinnings (electroencephalography (EEG), electrocardiography (ECG), endogenous melatonin rhythms and actigraphy) of a complaint of poor sleep and their relation to the occurrence of PLEs. We then refocus on which parameters of sleep are most integral to the sleep-PLE relationship and close with an investigation of how Hypothalamic Pituitary Adrenal (HPA) axis activity may further our knowledge of this relationship. The findings of this thesis demonstrate specificity in the parameters of sleep shown to impact certain PLEs. The importance of objective sleep and biologically driven measures in this line of research are underscored, with group differences in EEG, ECG and melatonin. This thesis also highlights dissociative symptomatology as a candidate mediator for the sleep-psychosis relationship, and emphasises the ties between paranoia and negative affect. Finally, this thesis also illuminates the challenges of examining the relationship between sleep and PLEs in isolation, and suggests that they must be considered within the broader framework of co-existing mental health problems.

Submitted by Fernando Marani (ef_marani@hotmail.com) on 2018-07-05T13:49:37Z No. of bitstreams: 1 Dissertação Mestrado_Fernando Marani versão final.pdf: 2309540 bytes, checksum: 52b048c82d6c31c4bcd9d2d5decb2623 (MD5) / Approved for entry into archive by Ana Paula Rimoli de Oliveira null (anapaula@foa.unesp.br) on 2018-07-06T12:19:32Z (GMT) No. of bitstreams: 1 marani_f_me_araca_int.pdf: 2309540 bytes, checksum: 52b048c82d6c31c4bcd9d2d5decb2623 (MD5) / Made available in DSpace on 2018-07-06T12:19:32Z (GMT). No. of bitstreams: 1 marani_f_me_araca_int.pdf: 2309540 bytes, checksum: 52b048c82d6c31c4bcd9d2d5decb2623 (MD5) Previous issue date: 2018-06-11 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Pesquisas têm sido realizadas para investigar a relação entre inflamações crônicas na cavidade oral e efeitos deletérios em diversos sistemas do organismo. A doença periodontal (DP) caracterizada como uma infecção e inflamação oral está associada à produção de citocinas inflamatórias, tais como fator de necrose tumoral-alfa (TNF-α) e interleucina-6 (IL-6), as quais aumentam a expressão dos osteoclastos, levando a um aumento da reabsorção óssea alveolar. Além da influência destas citocinas na perda óssea alveolar, evidências científicas apontam que a falta do hormônio melatonina também pode contribuir para uma maior reabsorção óssea. A melatonina é um poderoso regulador da homeostase de diversos tecidos. Assim, este hormônio pode ter um importante papel na proteção de tecidos lesionados, podendo ser visto, como um possível coadjuvante no tratamento de doenças da cavidade oral devido principalmente sua ação antioxidante e imunomoduladora. Portanto, o objetivo deste estudo foi verificar o efeito da suplementação da melatonina na reabsorção óssea alveolar em ratos com doença periodontal e pinealectomizados (PNX), avaliando: 1) concentrações plasmáticas de TNF-α e IL-6 pelo método de ELISA; 2) marcadores ósseos como a fosfatase ácida resistente ao tartarato (TRAP) e Osteocalcina (OCN) por meio de técnica imunoistoquímica; 3) histomorfometria da região comprometida pela DP pelo escaneamento no microtomógrafo em 3D (Micro-CT) (modelo 1172 SkyScan®). Para tanto, oitenta (80) ratos Wistar machos com 40 dias de idade foram distribuídos aleatoriamente em 8 grupos (n=10): controle (CN), doença periodontal (DP), pinealectomizados (PNX), pinealectomizados com doença periodontal (PNXDP), controle com melatonina (CNMEL), doença periodontal com melatonina (DPMEL), pinealectomizados com melatonina (PNXMEL) e pinealectomizados com doença periodontal e com melatonina (PNXDPMEL). A DP foi induzida após 20 dias da pinealectomia por ligadura com fio de seda ao redor dos primeiros molares mandibulares. Após 28 dias da indução da DP, os experimentos foram realizados. A análise estatística foi realizada por análise de variância Three-way (ANOVA), seguida pelo teste de Tukey e para as análises de imunoistoquímicas pelo teste estatístico não paramétrico de Kruskal Wallis. O nível de significância adotado foi de 5% (alfa=5%). Os resultados evidenciaram um aumento de mediador pró-inflamatório TNF-α tanto nos animais com DP como PNX. Apenas os grupos com DP (DP e PNXDP) apresentaram maior reabsorção óssea alveolar devido uma maior atividade dos osteoclastos comparado a dos osteoblastos evidenciado pelo aumento do marcador de reabsorção, fosfatase ácida resistente ao tartarato (TRAP), e diminuição do marcador de formação, osteocalcina (OCN) como também pelos resultados histomorfométricos. Por outro lado, os animais tratados com melatonina não apresentaram alteração na concentração plasmática de TNF-α e perda óssea alveolar. Com base nos resultados do presente estudo, verificou-se que os animais pinealectomizados e com DP apresentaram elevada concentração de TNF-α, mas a perda óssea alveolar ocorreu apenas nos animais com DP. A pinealectomia não promoveu alteração óssea como também não agravou esse parâmetro em animais com DP. A suplementação com melatonina promoveu diminuição de TNF-α nos animais pinealectomizados e com DP. Em todos os grupos com DP a melatonina protegeu-os da reabsorção óssea alveolar. Portanto, estes resultados demonstram que a melatonina é eficiente no controle tanto da reabsorção óssea alveolar como da concentração plasmática de TNF-α em ratos com DP e PNX, demonstrando sua importância local e sistêmica. / ABSTRACT Researches has been conducted to investigate the relationship between chronic inflammation in the oral cavity and deleterious effects on various systems of the body. Periodontal disease (PD) characterized as an infection and oral inflammation is associated with the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which increase the expression of osteoclasts, leading to an increase in alveolar bone resorption. In addition to the influence of these cytokines on alveolar bone loss, scientific evidence indicates that the lack of the hormone melatonin may also contribute to a greater bone resorption. Melatonin is a powerful regulator of homeostasis of various tissues. Thus, this hormone may have an important role in the protection of injured tissues, and can be seen as a possible adjuvant in the treatment of diseases of the oral cavity mainly due to its antioxidant and immunomodulatory action. Therefore, the objective of this study was to verify the effect of melatonin supplementation on alveolar bone resorption in rats with periodontal disease and pinealectomized (PNX), evaluating: 1) plasma concentrations of TNF-α and IL-6 by the ELISA method; 2) bone markers such as tartrate resistant acid phosphatase (TRAP) and Osteocalcin (OCN) by immunohistochemical technique; 3) histomorphometry of the region compromised by PD by scanning in the microtomograph in 3D (Micro-CT) (model 1172 SkyScan®). Therefore, eighty (80) Wistar male rats of 40 days old were randomly distributed into 8 groups (n= 10): control (CN), periodontal disease (PD), pinealectomized (PNX) pinealectomized with periodontal disease (PNXPD), control with melatonin (CNMEL), periodontal disease with melatonin (PDMEL) pinealectomized with melatonin (PNXMEL) and pinealectomized with periodontal disease and melatonin (PNXPDMEL). PD was induced after 20 days of pinealectomy by ligation with silk thread around the first mandibular molars. After 28 days of induction of DP, the experiments were performed. Statistical analysis was performed by Three-way analysis of variance (ANOVA), followed by the Tukey's test and for the immunohistochemical analyzes by the non-parametric statistical test of Kruskal Wallis. The level of significance was 5% (alpha = 5%). The results evidenced an increase of proinflammatory mediator TNF-α in both PD and PNX animals. Only the groups with PD (PD and PNXPD) presented greater alveolar bone resorption due to a higer activity of the osteoclasts compared to the osteoblasts evidenced by the increase of the resorption marker, tartrate resistant acid phosphatase (TRAP), and decrease of the formation marker osteocalcin (OCN) as well as histomorphometric results. On the other hand, in animals treated with melatonin there was no change in plasma TNF-α concentration and alveolar bone loss. Based on the results of the present study, pinealectomized and PD animals showed high concentration of TNF-α, but alveolar bone loss occurred only in animals with PD. Pinealectomy did not promote bone alteration, nor did it aggravate this parameter in animals with PD. Supplementation with melatonin promoted decreased TNF-α in pinealectomized and PD animals. In all groups with PD, melatonin protected them from alveolar bone resorption. Therefore, these results demonstrate that melatonin is efficient in controlling both alveolar bone resorption and plasma TNF-α concentration in rats with PD and PNX, demonstrating its local and systemic importance.

"Life" may be characterized as a controlled stationary flow equilibrium, maintained by energy consuming chemical reactions. The physiological functioning of these life systems include at least 28 of the elements isolated on the periodic table thus far, most of which are metals. However, as with Paracelsus Principle: "The dose makes the poison", there exists a definite link between metal levels, essential and toxic, and the onset of neurodegenerative diseases. The economic costs of brain dysfunction are enormous, but this pales in comparison to the staggering emotional toll on the victims themselves and their families. In an attempt to improve the understanding of the causes of neurodegeneration, this study focuses on one potential aspect: the possible link between metals and neurotransmitter homeostasis utilising a variety of electronanalytical techniques. Adsorptive cathodic stripping voltammetry was employed to investigate the binding affinities and complex formation of melatonin and its precursor serotonin with calcium, potassium, sodium, lithium and aluminium. The results showed that all the metals studied formed complexes with both pineal indoleamines. However, the stability and affmity of the ligands toward the various metals varied greatly. The study suggests a further role for melatonin, that of metalloregulator and possible metal detoxifier in the brain, the in vivo studies which followed will further substantiate this notion. This research additionally focused on the cholinergic system, in particular acetylcholine complex formation studies with mercury, lead, cadmium, copper and zinc using the adsorptive cathodic stripping voltammetry method. The formation and characterisation of a solid mercury-acetylcholine complex lent further strength to the in situ electrochemical complex formation observed. The results showed the preference of acetylcholine for environmentally toxic heavy metals (such as Cd²⁺) over those divalent cations that occur naturally in the body. The possible metalloregulatory role melatonin played in the three brain regIOns: cerebellum, cortex and corpus striatum of male Wistar rats was studied as an in vivo extension of the earlier in vitro studies. Anodic stripping voltammetry was employed to detect metal levels present. The results showed that daily injections of melatonin was responsible for significantly decreasing copper(I), cadmium(II) and lead(II) levels in various regions of the rat brain of those animals that had undergone a pinealectomy in comparison to the saline injected group having undergone the same treatment. Histological and electrochemical stripping techniques were applied to investigate the implications of high A1³⁺ levels in the brain regions, particularly the hippocampus. Melatonin showed signs of promise in indirect symptom alleviation and by significantly decreasing A1³⁺ levels in rats that had been dosed with melatonin prior to A1³⁺ treatments in comparison with the control groups. Finally a preliminary study outlining a method for the production of a calcium selective microelectrode was undertaken. Further work is still needed to optimise the microelectrode production as well as its possible applications. However, whilst the overall conclusions of this entire multidisciplinary study may indeed only be in effect one piece of a very large puzzle on neurodegenerative diseases, this piece will no doubt serve as a building block for further ideas and work in this field.