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Rev. Nutr. (Online) ; 35: e220058, 2022. tab, graf
Article in English | LILACS | ID: biblio-1406918


ABSTRACT Objective The aim of the present study was to evaluate the consumption of risk and protective foods for chronic noncommunicable diseases and to investigate associations with anthropometric parameters and body composition in individuals with Parkinson's disease. Methods A case-series study was conducted with 79 adult and elderly patients of both genders in outpatient care. Food intake was evaluated using a food frequency questionnaire for the identification of foods with greater daily consumption, stratified by gender. The consumption frequency of each food was converted into scores of two food groups characteristics: risk and protection. The conceptual model took into account sociodemographic, behavioral and anthropometric variables as well as body composition. Results A total of 72.1% of the participants in the sample had excess weight based on the body mass index and 43.5% had excess body fat. The consumption of protective foods was greater among individuals with a higher body mass index and with a greater rate of body fat. Conclusion The data indicate a situation of reverse causality and reveal the complexity of the relationship among food intake, body fat and chronic noncommunicable diseases.

RESUMO Objetivo Este estudo visou avaliar o consumo de alimentos de risco e proteção para as doenças crônicas não transmissíveis e sua associação com parâmetros antropométricos e de composição corporal em pacientes com doença de Parkinson. Métodos Estudo do tipo série de casos, com 79 pacientes adultos e idosos, de ambos os sexos, atendidos ambulatorialmente. O consumo alimentar desses pacientes foi avaliado por um questionário de frequência alimentar, sendo identificados inicialmente os alimentos com maior frequência de consumo diário por sexo e, em seguida, a frequência de consumo de cada alimento foi convertida em escores, sendo constituídos dois grupos de alimentos: risco e proteção. O modelo conceitual considerou variáveis sociodemográficas, comportamentais, antropométricas e de composição corporal. Resultados Ao todo, 72,1% dos pacientes apresentaram excesso de peso segundo o índice de massa corporal e 43,5% apresentaram excesso de gordura corporal. O consumo de alimentos protetores foi maior nos pacientes com maior índice de massa corporal e maior percentual de gordura corporal. Conclusão Os dados apontam para uma condição de causalidade reversa e revelam a complexidade envolvida na relação entre consumo alimentar, gordura corporal e doenças crônicas não transmissíveis.

Humans , Male , Female , Middle Aged , Aged , Parkinson Disease/metabolism , Body Composition , Eating , Body Mass Index , Overweight/physiopathology , Obesity/physiopathology
Article in Chinese | WPRIM | ID: wpr-935788


Objective: To observe the dynamic changes of brainstem locus coeruleus (LC) damage in Parkinson' s disease (PD) -like mice by paraquat (PQ) . Methods: In October 2019, 36 male C57BL/6 mice were randomly divided into the exposure group and the control group, with 18 mice in each group. The mice in the exposure group were given intraperitoneal injection of 15 mg/kg PQ, and the mice in the control group were given intraperitoneal injection of 0.9% saline, twice a week for 8 weeks. Neurobehavioral changes (pole climbing test, swimming test, open field test, tail hanging test, high plus maze test and water maze test) were observed at 4 weeks, 6 weeks and 8 weeks, respectively, and the changes of motor ability, emotion and cognitive function were evaluated. The brain tissue of mice were taken and stained with Hematoxylin-Eosin (HE) to observe the pathological changes of LC. Nissl staining was used to detect the changes of neuronal Nissl bodies in LC. Immunohistochemistry (IHC) staining was used to detect the expression of neuron nuclear antigen (NeuN) , dopamine (DA) neurons and norepinephrine (NE) neuron markers tyrosine hydroxylase (TH) , α-synuclein (α-syn) in substantia nigra (SN) and LC. The expression levels of NeuN, TH and α-syn in the midbrain and brainstem were detected by Western blotting. TUNEL staining was used to detect neuronal apoptosis in LC. Results: Compared with the 4th week of PQ exposure group, the time of pole climbing and swimming immobility were gradually increased, the ratio of open arm residence time of high plus maze test and the number of times of the platform and the residence time of platform quadrant in water maze test were gradually decreased (P<0.05) in the exposure group with the progress of exposure time. The results of HE and Nissl staining showed that the neurons in LC gradually arranged loosely, the nucleus were deeply stained, the cytoplasm was pyknosis, and the number of Nissl bodies gradually decreased (P<0.05) in the exposure group with the progress of exposure time. IHC results showed that the number of NeuN and TH positive cells in SN and LC of mice were gradually decreased, and the positive expression of α-syn was gradually increased (P<0.05) in the exposure group with the progress of exposure time. Western blotting results showed that the expression levels of NeuN and TH in the midbrain and brainstem were gradually decreased, and the expression level of α-syn was gradually increased (P<0.05) in the exposure group with the progress of exposure time. TUNEL staining showed that the apoptosis rates of neurons in LC were gradually increased (P<0.05) in the exposure group with the progress of exposure time. Conclusion: PQ induces progressive damage in the LC area of PD-like mice, which may be caused by the abnormal accumulation of pathological α-syn in the LC area.

Animals , Dopaminergic Neurons , Locus Coeruleus/pathology , Male , Mice , Mice, Inbred C57BL , Paraquat/toxicity , Parkinson Disease/metabolism , Substantia Nigra , Tyrosine 3-Monooxygenase/metabolism
Article in Chinese | WPRIM | ID: wpr-940983


OBJECTIVE@#To explore whether the using of mimetic peptide Gap27, a selective inhibitor of connexin 43 (Cx43), could block the death of dopamine neurons and influence the expression of Cx43 in 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease mouse models.@*METHODS@#Eighteen C57BL/6 mice were randomly divided into control group, 6-OHDA group and 6-OHDA+Gap27 group, with 6 mice in each group. Bilateral substantia nigra stereotactic injection was performed. The control group was injected with ascorbate solution, 6-OHDA group was injected with 6-OHDA solution, and 6-OHDA+Gap27 group was injected with 6-OHDA and Gap27 mixed solution. Immuno-histochemical staining was used to detect the number of dopamine neurons, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of Cx43 messenger ribonucleic acid (mRNA), immuno-fluorescence staining was used to detect the distribution of Cx43 protein, the contents of Cx43 protein and Cx43 phosphorylation at serine 368 (Cx43-ps368) in mouse midbrain were detected by Western blot.@*RESULTS@#After injection of 6-OHDA, numerous dopamine neurons in substantia nigra died as Cx43 content increased, Cx43-ps368 content decreased. Mixing Gap27 while injecting 6-OHDA could reduce the number of death dopamine neurons and weaken the changes of Cx43 and Cx43-ps368 content caused by 6-OHDA. The number of tyrosine hydroxylase (TH) immunoreactive positive neurons in 6-OHDA group decreased to 27.7% ± 0.02% of the control group (P < 0.01); The number of TH immunoreactive positive neurons in 6-OHDA+Gap27 group was (1.64±0.16) times higher than that in 6-OHDA group (P < 0.05); The content of total Cx43 protein in 6-OHDA group was (1.44±0.07) times higher than that in 6-OHDA+Gap27 group (P < 0.05) while (1.68±0.07) times higher than that in control group (P < 0.01). In 6-OHDA group, the content of Cx43-ps368 protein and its proportion in total Cx43 protein were significantly lower than that in 6-OHDA+Gap27 group (P < 0.05).@*CONCLUSION@#In 6-OHDA mouse models, mimetic peptide Gap27 played a protective role in reducing the damage to substantia nigra dopamine neurons, which was induced by 6-OHDA. The overexpression of Cx43 protein might have neurotoxicity to dopamine neuron. Meanwhile, decreasing Cx43 protein level and keeping Cx43-ps368 protein level may be the protective mechanisms of Gap27.

Animals , Connexin 43/pharmacology , Disease Models, Animal , Dopaminergic Neurons/metabolism , Mice , Mice, Inbred C57BL , Oxidopamine/metabolism , Parkinson Disease/metabolism , Peptides/pharmacology , Tyrosine 3-Monooxygenase/pharmacology
Biol. Res ; 53: 01, 2020. graf
Article in English | LILACS | ID: biblio-1089072


BACKGROUND: Long non-coding RNA small molecule RNA host gene 1 (SNHG1) was previously identified to be relevant with Parkinson's disease (PD) pathogenesis. This work aims to further elucidate the regulatory networks of SNHG1 involved in PD. Methods: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-hydrochloride (MPTP)-induced mice and 1-methyl-4-phenylpyridinium (MPP+)-treated SH-SY5Y cells were respectively constructed as the in vivo and in vitro PD models. Expression levels of SNHG1 and miR-153-3p were detected by qRT-PCR. Protein expression levels of phosphate and tension homology deleted on chromosome ten (PTEN) were measured by western blotting assay. Cell viability and apoptosis were determined by MTT and flow cytometry assays. The interactions among SNHG1, miR-153-3p and PTEN were identified by luciferase reporter assay, RNA immunoprecipitation, and/or RNA pull-down analysis. RESULTS: Increased SNHG1 expression was found in midbrain of MPTP-induced PD mice and MPP+-treated SH-SY5Y cells. Overexpression of SNHG1 lowered viability and enhanced apoptosis in MPP+-treated SH-SY5Y cells. Moreover, SNHG1 acted as a molecular sponge to inhibit the expression of miR-153-3p. Furthermore, miR-153-3p-mediated suppression of MPP+-induced cytotoxicity was abated following SNHG1 up-regulation. Additionally, PTEN was identified as a direct target of miR-153-3p, and SNHG1 could serve as a competing endogenous RNA (ceRNA) of miR-153-3p to improve the expression of PTEN. Besides, enforced expression of PTEN displayed the similar functions as SNHG1 overexpression in regulating the viability and apoptosis of MPP+-treated SH-SY5Y cells. Finally, SNHG1 was found to activate PTEN/AKT/mTOR signaling pathway in SH-SY5Y cells by targeting miR-153-3p. CONCLUSION: SNHG1 aggravates MPP+-induced cellular toxicity in SH-SY5Y cells by regulating PTEN/AKT/mTOR signaling via sponging miR-153-3p, indicating the potential of SNHG1 as a promising therapeutic target for PD.

Animals , Male , Mice , Parkinson Disease/metabolism , 1-Methyl-4-phenylpyridinium/toxicity , PTEN Phosphohydrolase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism , RNA, Long Noncoding/metabolism , Parkinson Disease/genetics , Transfection , Signal Transduction , Cells, Cultured , Gene Expression Regulation , Blotting, Western , Apoptosis , MicroRNAs , Disease Models, Animal , Real-Time Polymerase Chain Reaction , RNA, Long Noncoding/genetics , Mice, Inbred C57BL
Arq. neuropsiquiatr ; 76(2): 67-70, Feb. 2018. graf
Article in English | LILACS | ID: biblio-888349


ABSTRACT Current understanding of the pathophysiology of Parkinson's disease suggests a key role of the accumulation of alpha-synuclein in the pathogenesis. This critical review highlights major landmarks, hypotheses and controversies about the origin and progression of synucleinopathy in Parkinson's disease, leading to an updated review of evidence suggesting the enteric nervous system might be the starting point for the whole process. Although accumulating and compelling evidence favors this theory, the remaining knowledge gaps are important points for future studies.

RESUMO O atual entendimento sobre a fisiopatologia da doença de Parkinson (DP) sugere um papel central do acúmulo de alfa-sinucleína na patogenia da DP Esta revisão crítica revisita marcos, teorias e controvérsias a respeito da origem e progressão da sinucleinopatia, apresentando uma atualização das principais evidências sugerindo que o sistema nervoso entérico seria o local inicial deste processo. Apesar das evidências a favor desta teoria serem crescentes e instigantes, as lacunas de conhecimento a este respeito são importantes pontos para estudos futuros.

Humans , Parkinson Disease/etiology , Parkinson Disease/metabolism , Parkinson Disease/pathology , Enteric Nervous System/metabolism , alpha-Synuclein/metabolism , Brain/metabolism , Enteric Nervous System/pathology , Disease Progression
Arq. neuropsiquiatr ; 74(9): 723-729, Sept. 2016. graf
Article in English | LILACS | ID: lil-796042


ABSTRACT The purpose of the present study was to investigate the effect of crocin on brain oxidative damage and memory deficits in a 6-hydroxydopamine (6-OHDA) model of Parkinson’s disease. Male Wistar rats were subjected to unilateral injection of 6-OHDA (16 µg) into the medial forebrain bundle and treated with crocin (30 and 60 mg/kg) for six weeks. The rats were tested for memory performance at six weeks after 6-OHDA infusion, and then were killed for the estimation of biochemical parameters. The increase in thiobarbituric acid reactive substances (TBARS) and nitrite levels in the hippocampus were observed in the 6-OHDA lesioned rats, which was accompanied by memory deficits in a passive avoidance test at the end of week 6. Moreover, treatment with crocin decreased TBARS and nitrite levels in the hippocampus, and improved aversive memory. The present study conclusively demonstrated that crocin acts as an antioxidant and anti-inflammatory agent in the hippocampus of parkinsonian rats and could improve aversive memory through its properties.

RESUMO O objetivo do presente estudo foi investigar o efeito da crocina no dano oxidativo cerebral e nos déficits de memória em um modelo 6-OHDA de doença de Parkinson. Ratos Wistar machos foram submetidos à injeção unilateral de 6-OHDA (16 μg) em MFB e tratados com crocina (30 e 60 mg/kg), durante 6 semanas. Os ratos foram testados quanto ao desempenho da memória 6 semanas após a infusão de 6-OHDA, e, em seguida, foram sacrificados para a estimativa dos parâmetros bioquímicos. O aumento nos níveis de TBARS e de nitrito no hipocampo foram observados em ratos 6-OHDA lesionados, acompanhado por déficits de memória em um teste de esquiva passiva no final da semana 6. Além disso, o tratamento com crocina diminuiu os níveis de nitrito e de TBARS no hipocampo e melhorou a memória aversiva. O presente estudo demonstrou conclusivamente que a crocina age como um antioxidante e um agente anti-inflamatório no hipocampo de ratos parkinsonianos e pode melhorar a memória aversiva através de suas propriedades.

Animals , Male , Parkinson Disease/drug therapy , Carotenoids/pharmacology , Cerebral Cortex/drug effects , Oxidative Stress/drug effects , Memory Disorders/prevention & control , Antioxidants/pharmacology , Parkinson Disease/physiopathology , Parkinson Disease/metabolism , Sulfhydryl Compounds/analysis , Lipid Peroxidation/drug effects , Random Allocation , Cerebral Cortex/physiopathology , Cerebral Cortex/metabolism , Oxidopamine , Thiobarbituric Acid Reactive Substances/analysis , Rats, Wistar , Disease Models, Animal , Glutathione Peroxidase/analysis , Glutathione Peroxidase/drug effects , Memory/drug effects , Memory/physiology , Memory Disorders/physiopathology , Memory Disorders/metabolism , Nitrites/analysis
Article in English | IMSEAR | ID: sea-157614


Parkinson’s disease (PD) is a progressive, neurological disease that mainly affects movements and occurs at older ages and is clinically characterized by resting tremor, rigidity, bradykinesia and postural imbalance. These clinical manifestations of PD are caused by a selective degeneration of dopamine-producing neurons in substantia nigra in the brain stem and the consequent dopamine shortage in the striatum. Oxidants and antioxidants related substances may contribute to the pathogenesis and the progression of Parkinson’s disease. Research can make great progress in understanding and further treating the PD. This study demonstrates significant variation of oxidants-antioxidants status in Parkinson’s disease. Oxidative stress plays a crucial role in progression of PD; however, oxidative stress is a cause or the consequence of PD is debatable. In our study we observed there is significant increase in the levels of serum Malondialdehyde (p< 0.001), Nitric oxide end products (p< 0.001), and significant decrease in the activity of Glutathione peroxidase (p< 0.001), Superoxide dismutase (p< 0.001), and Catalase (p< 0.001) in PD patients as compared with controls. Further Vitamin C (p< 0.05), Vitamin E (p< 0.05) significantly decreased, but Uric acid levels (p> 0.05) remain unchanged and this may be due to compensatory mechanism of body against oxidative stress, which not allowed much alteration in other parameter in the PD patients as compared with controls.

Antioxidants/metabolism , Catalase , Glutathione Peroxidase , Nitric Oxide , Oxidative Stress/physiology , Oxidants/metabolism , Parkinson Disease/chemistry , Parkinson Disease/metabolism , Superoxide Dismutase , Uric Acid
Article in English | WPRIM | ID: wpr-161111


A double toxin-double lesion strategy is well-known to generate a rat model of striatonigral degeneration (SND) such as multiple system atrophy-parkinsonian type. However, with this model it is difficult to distinguish SND from Parkinson's disease (PD). In this study, we propose a new rat model of SND, which is generated by simultaneous injection of 6-hydroxydopamine into the medial forebrain bundle and quinolinic acid into the striatum. Stepping tests performed 30 min after intraperitoneal L-dopa administration at 6 weeks post-surgery revealed an L-dopa response in the PD group but not the SND group. Apomorphine-induced rotation tests revealed no rotational bias in the SND group, which persisted for 2 months, but contralateral rotations in the PD group. MicroPET scans revealed glucose hypometabolism and dopamine transporter impairment on the lesioned striatum in the SND group. Tyrosine hydroxylase immunostaining in the SND group revealed that 74.7% of nigral cells on the lesioned side were lost after lesion surgery. These results suggest that the proposed simultaneous double toxin-double lesion method successfully created a rat model of SND that had behavioral outcomes, multitracer microPET evaluation, and histological aspects consistent with SND pathology. This model will be useful for future study of SND.

Animals , Apomorphine/pharmacology , Behavior, Animal/drug effects , Corpus Striatum/drug effects , Disease Models, Animal , Dopamine Plasma Membrane Transport Proteins/metabolism , Glucose/metabolism , Injections, Intraperitoneal , Levodopa/pharmacology , Male , Medial Forebrain Bundle/drug effects , Oxidopamine/toxicity , Parkinson Disease/metabolism , Positron-Emission Tomography , Quinolinic Acid/toxicity , Rats , Rats, Wistar , Striatonigral Degeneration/chemically induced , Touch/drug effects
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 34(supl.2): s194-s205, Oct. 2012.
Article in English | LILACS | ID: lil-662767


Neurodegenerative disorders are undoubtedly an increasing problem in the health sciences, given the increase of life expectancy and occasional vicious life style. Despite the fact that the mechanisms of such diseases are far from being completely understood, a large number of studies that derive from both the basic science and clinical approaches have contributed substantial data in that direction. In this review, it is discussed several frontiers of basic research on Parkinson´s and Alzheimer´s diseases, in which research groups from three departments of the Institute of Biomedical Sciences of the University of São Paulo have been involved in a multidisciplinary effort. The main focus of the review involves the animal models that have been developed to study cellular and molecular aspects of those neurodegenerative diseases, including oxidative stress, insulin signaling and proteomic analyses, among others. We anticipate that this review will help the group determine future directions of joint research in the field and, more importantly, set the level of cooperation we plan to develop in collaboration with colleagues of the Nucleus for Applied Neuroscience Research that are mostly involved with clinical research in the same field.

Os transtornos neurodegenerativos são, sem dúvida, um problema crescente nas ciências da saúde, dado o aumento da expectativa de vida e de estilos de vida pouco saudáveis. Embora os mecanismos de tais doenças ainda estejam longe de ser esclarecidos, vários estudos que derivam tanto da ciência básica quanto de abordagens clínicas contribuíram nessa direção. Na presente revisão, são discutidas linhas de frente da pesquisa básica sobre as doenças de Parkinson e Alzheimer, em que grupos de pesquisas de três departamentos do Instituto de Ciências Biomédicas da Universidade de São Paulo estão envolvidos em um esforço multidisciplinar. O foco principal desta revisão envolve os modelos animais desenvolvidos para se estudar os aspectos celulares e moleculares daquelas doenças neurodegenerativas, incluindo o estresse oxidativo, a sinalização da insulina e as análises proteômicas, dentre outros. Antecipamos que esta revisão irá auxiliar o grupo a determinar as futuras direções da pesquisa conjunta nessa área e, o mais importante, estabelecer o nível de cooperação que planejamos desenvolver juntamente com colegas do Núcleo de Apoio à Pesquisa em Neurociência Aplicada que estão envolvidos com pesquisa clínica na mesma área.

Animals , Humans , Alzheimer Disease/metabolism , Parkinson Disease/metabolism , Alzheimer Disease/etiology , Biomarkers/analysis , Brain/pathology , Disease Models, Animal , Exercise/physiology , NADPH Oxidases/metabolism , Oxidative Stress/physiology , Parkinson Disease/etiology , Peptides/analysis , Proteomics
Article in English | WPRIM | ID: wpr-93421


Autophagy is a dynamic cellular pathway involved in the turnover of proteins, protein complexes, and organelles through lysosomal degradation. The integrity of postmitotic neurons is heavily dependent on high basal autophagy compared to non-neuronal cells as misfolded proteins and damaged organelles cannot be diluted through cell division. Moreover, neurons contain the specialized structures for intercellular communication, such as axons, dendrites and synapses, which require the reciprocal transport of proteins, organelles and autophagosomes over significant distances from the soma. Defects in autophagy affect the intercellular communication and subsequently, contributing to neurodegeneration. The presence of abnormal autophagic activity is frequently observed in selective neuronal populations afflicted in common neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. These observations have provoked controversy regarding whether the increase in autophagosomes observed in the degenerating neurons play a protective role or instead contribute to pathogenic neuronal cell death. It is still unknown what factors may determine whether active autophagy is beneficial or pathogenic during neurodegeneration. In this review, we consider both the normal and pathophysiological roles of neuronal autophagy and its potential therapeutic implications for common neurodegenerative diseases.

Alzheimer Disease/metabolism , Animals , Autophagy/physiology , Humans , Huntington Disease/metabolism , Models, Biological , Neurodegenerative Diseases/metabolism , Neurons/cytology , Parkinson Disease/metabolism
Article in English | WPRIM | ID: wpr-187631


Parkinson's disease (PD) is characterized by selective and progressive degeneration of dopamine (DA)-producing neurons in the substantia nigra pars compacta (SNpc) and by abnormal aggregation of alpha-synuclein. Previous studies have suggested that DA can interact with alpha-synuclein, thus modulating the aggregation process of this protein; this interaction may account for the selective vulnerability of DA neurons in patients with PD. However, the relationship between DA and alpha-synuclein, and the role in progressive degeneration of DA neurons remains elusive. We have shown that in the presence of DA, recombinant human alpha-synuclein produces non-fibrillar, SDS-resistant oligomers, while beta-sheet-rich fibril formation is inhibited. Pharmacologic elevation of the cytoplasmic DA level increased the formation of SDS-resistant oligomers in DA-producing neuronal cells. DA promoted alpha-synuclein oligomerization in intracellular vesicles, but not in the cytosol. Furthermore, elevation of DA levels increased secretion of alpha-synuclein oligomers to the extracellular space, but the secretion of monomers was not changed. DA-induced secretion of alpha-synuclein oligomers may contribute to the progressive loss of the dopaminergic neuronal population and the pronounced neuroinflammation observed in the SNpc in patients with PD.

Blotting, Western , Cell Line, Tumor , Dopamine/metabolism , Humans , Levodopa/pharmacology , Neurons/metabolism , Parkinson Disease/metabolism , Substantia Nigra/metabolism , alpha-Synuclein/biosynthesis
Rev. salud pública ; 9(2): 308-314, abr.-jun. 2007.
Article in Spanish | LILACS | ID: lil-457939


Con base en un caso personal estudiado en forma diaria y continua se deduce que la enfermedad de Parkinson idiopática es una autointoxicación endógena por alteraciones en la biosíntesis de la morfina, y se propone la determinación de los niveles de ésta en la sangre tanto en los parkinsonianos antes de cualquier tratamiento y, con el fin de establecer su diagnóstico preclínico, en los depresivos que constituyen el grupo mas afectado por la enfermedad de Parkinson.

Based on a day-by-day, in-depth study of a clinical case, it was deduced that Parkinson's disease results in autointoxication, due to damage to morphine biosynthesis. Blood morphine levels should be studied in patients suffering from Parkinson's disease before treatment as well as in depressive patients (being the group most affected by Parkinson´s disease) to achieve early preclinical diagnosis.

Humans , Morphine/metabolism , Parkinson Disease/metabolism
Braz. j. med. biol. res ; 40(1): 89-96, Jan. 2007. ilus, graf
Article in English | LILACS | ID: lil-439667


There is a great concern in the literature for the development of neuroprotectant drugs to treat Parkinson's disease. Since anesthetic drugs have hyperpolarizing properties, they can possibly act as neuroprotectants. In the present study, we have investigated the neuroprotective effect of a mixture of ketamine (85 mg/kg) and xylazine (3 mg/kg) (K/X) on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine (6-OHDA) rat models of Parkinson's disease. The bilateral infusion of MPTP (100 æg/side) or 6-OHDA (10 æg/side) into the substantia nigra pars compacta of adult male Wistar rats under thiopental anesthesia caused a modest (~67 percent) or severe (~91 percent) loss of tyrosine hydroxylase-immunostained cells, respectively. On the other hand, an apparent neuroprotective effect was observed when the rats were anesthetized with K/X, infused 5 min before surgery. This treatment caused loss of only 33 percent of the nigral tyrosine hydroxylase-immunostained cells due to the MPTP infusion and 51 percent due to the 6-OHDA infusion. This neuroprotective effect of K/X was also suggested by a less severe reduction of striatal dopamine levels in animals treated with these neurotoxins. In the working memory version of the Morris water maze task, both MPTP- and 6-OHDA-lesioned animals spent nearly 10 s longer to find the hidden platform in the groups where the neurotoxins were infused under thiopental anesthesia, compared to control animals. This amnestic effect was not observed in rats infused with the neurotoxins under K/X anesthesia. These results suggest that drugs with a pharmacological profile similar to that of K/X may be useful to delay the progression of Parkinson's disease.

Animals , Male , Rats , Anesthetics, Combined/administration & dosage , Ketamine/administration & dosage , Neuroprotective Agents/administration & dosage , Parkinson Disease/drug therapy , Substantia Nigra/drug effects , Xylazine/administration & dosage , Anesthetics, Combined/pharmacology , Biogenic Monoamines/metabolism , Corpus Striatum/metabolism , Disease Models, Animal , Immunohistochemistry , Ketamine/pharmacology , Maze Learning/drug effects , Maze Learning/physiology , Neuroprotective Agents/pharmacology , Oxidopamine , Parkinson Disease/metabolism , Parkinson Disease/pathology , Rats, Wistar , Substantia Nigra/metabolism , Substantia Nigra/pathology , Thiopental/administration & dosage , Thiopental/pharmacology , /metabolism , Xylazine/pharmacology
Arq. neuropsiquiatr ; 64(4): 1019-1022, dez. 2006.
Article in English, Portuguese | LILACS | ID: lil-439763


We report a 67-year-old man with Parkinson's disease for 9 years who developed compulsive use of levodopa. This phenomenon is the main feature of the dopamine dysregulation syndrome. Other related symptoms presented by our patient were mood fluctuation and increased writing activity suggestive of punding.

Relatamos sobre um homem de 67 anos de idade com doença de Parkinson por 9 anos e que desenvolveu uso compulsivo de levodopa. Esse fenômeno é a principal característica da síndrome de desregulação dopaminérgica. Outros sintomas apresentados pelo paciente foram flutuações do humor e atividade de escrita aumentada, comportamento este sugestivo de punding.

Aged , Humans , Male , Antiparkinson Agents/adverse effects , Dopamine/metabolism , Levodopa/adverse effects , Mood Disorders/chemically induced , Parkinson Disease/metabolism , Substance-Related Disorders/diagnosis , Antiparkinson Agents/therapeutic use , Levodopa/therapeutic use , Parkinson Disease/drug therapy , Syndrome , Substance-Related Disorders/complications
Arq. neuropsiquiatr ; 64(3a): 628-634, set. 2006. ilus, graf, tab
Article in Portuguese, English | LILACS | ID: lil-435602


INTRODUÇÃO: Radiotraçadores para neuroimagem de transportador de dopamina (TDA) foram desenvolvidos para estimar a perda de neurônios dopaminérgicos in vivo na doença de Parkinson (DP). OBJETIVO: Avaliar a densidade de TDA in vivo utilizando [99mTc]-TRODAT-1 (INER-Taiwan) e SPECT em uma população de pacientes brasileiros com DP. MÉTODO: Quinze pacientes com DP e 15 controles saudáveis pareados realizaram exames de SPECT com [99mTc]-TRODAT-1 (INER-Taiwan). Estimativas da densidade de TDA estriatal foram calculadas usando potencial de ligação (PL). Pacientes foram avaliados com escalas para PD. RESULTADOS: Pacientes com DP apresentaram redução significativa do PL-TDA (0,38±0,12) comparado aos controles (0,84±0,16, p<0,01). Foi possível discriminar casos de DP de controles com uma sensibilidade de 100 por cento e especificidade de 100 por cento. Foram obtidas correlações negativas entre PL-TDA e escalas de severidade da DP (rho= -0,7, p<0,001) e disfunção motora (rho= -0,8, p<0,001). CONCLUSÃO: Exames de SPECT com [99mTc]-TRODAT-1 foram capazes de discriminar pacientes com DP de controles. Esta técnica é um instrumento útil para medir a densidade de TDA e pode ser utilizado para clínica e pesquisa no Brasil.

BACKGROUND: Dopamine transporter (DAT) neuroimaging radiotracers were developed to estimate dopamine neuronal loss in vivo in ParkinsonÆs disease (PD). OBJECTIVE: To evaluate DAT density in vivo using [99mTc]-TRODAT-1 and single photon computerized tomography (SPECT) in a population of Brazilian PD. METHOD: Fifteen PD patients and 15 matched healthy controls scanned with [99mTc]-TRODAT-1 (INER-Taiwan) and SPECT. Estimates of striatum DAT density were calculated using binding potential (BP). Patients were assessed with PD scales. RESULTS: PD patients had significantly lower striatal DAT-BP (mean±SD) (0.38±0.12) compared to controls (BP=0.84±0.16; p<0.01). A 100 percent sensitivity and 100 percent specificity was obtained to discriminate PD cases from controls. Negative correlations between striatal DAT-BP and PD severity (rho= -0.7, p<0.001) and motor scales (rho= -0.80, p<0.001) were found. CONCLUSION: [99mTc]TRODAT-1 SPECTs scanning was able to discriminate PD patients from controls. The technique is a powerful instrument to measure DAT density that can be used in clinical and research settings in Brazil.

Humans , Male , Female , Adult , Middle Aged , Dopamine Plasma Membrane Transport Proteins/metabolism , Organotechnetium Compounds , Parkinson Disease , Tomography, Emission-Computed, Single-Photon/methods , Tropanes , Case-Control Studies , Parkinson Disease/metabolism , Reproducibility of Results , Radiopharmaceuticals , Sensitivity and Specificity , Severity of Illness Index
Rev. méd. Chile ; 134(7): 893-901, jul. 2006. ilus, tab
Article in Spanish | LILACS | ID: lil-434592


Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Dopamine deficit is the cornerstone of its clinical manifestations. Levodopa, the main treatment for this condition, was first used for PD more than 40 years ago and today it still is the most powerful treatment for this disease. In recent years many advances have been made for understanding of the neurochemical mechanisms of this drug. Furthermore, new insights about the genesis of motor complications secondary to its use are known, specially related with the mode of its administration. This article updates the pharmacology of levodopa and its implications for the pathophysiology and treatment of PD. The new available presentations of levodopa are also reviewed. The implications of these advances for the treatment of this disease are commented.

Humans , Antiparkinson Agents/therapeutic use , Dopamine Agents/therapeutic use , Levodopa/therapeutic use , Parkinson Disease/drug therapy , Antiparkinson Agents/adverse effects , Antiparkinson Agents/pharmacokinetics , Chile , Dopamine Agents/adverse effects , Dopamine Agents/pharmacokinetics , Dyskinesia, Drug-Induced/etiology , Levodopa/adverse effects , Levodopa/pharmacokinetics , Parkinson Disease/metabolism , Parkinson Disease/physiopathology
Neurol India ; 2004 Sep; 52(3): 332-7
Article in English | IMSEAR | ID: sea-121411


BACKGROUND: Iron accumulation in substantia nigra pars compacta (SNpc) and related intensity and volumetric changes in patients with idiopathic Parkinson's disease (PD) has been reported previously. There are only a few studies evaluating the relation between neuroradiological findings and clinical scores, with contradictory results. AIMS: In this study we aimed to measure the iron-rich brain areas of PD patients and healthy subjects with T2-weighted magnetic resonance imaging (MRI) and to evaluate the relation between the clinical scores of PD patients and these imaging results. METHODS AND MATERIALS: T2-weighted MRI findings were studied in 20 patients with PD and 16 healthy controls. The width of SNpc, putamen volume, and the intensity of the basal ganglia were measured. Unified Parkinson's Disease Rating Scale (UPDRS) was used for evaluating the clinical status. STATISTICAL ANALYSES: Mann Whitney U test for group comparisons, Wilcoxon sign rank test for comparisons within the patient group, and Spearman's rank correlation coefficient for analyses of correlations were used. RESULTS: Mean SNpc and dentate nucleus intensities were lower in PD patients than healthy subjects. Mean SNpc width and putamen volumes were lower in patients. Decrease in the intensity of mean SNpc correlated with high UPDRS and rigidity scores. CONCLUSION: The results of our study reflect the increase in iron accumulation and oxidative stress in the SNpc in Parkinson's disease. The decrease in the intensity of SNpc correlates with poor clinical scores.

Aged , Brain Chemistry , Female , Humans , Iron/metabolism , Magnetic Resonance Imaging , Male , Middle Aged , Neurologic Examination , Neuropsychological Tests , Parkinson Disease/metabolism , Prospective Studies , Substantia Nigra/metabolism
Article in Portuguese | LILACS | ID: lil-358116


O autor apresenta uma visão geral da literatura atual sobre homocisteína como um fator de risco para os transtornos neuropsiquiátricos. Foram pesquisados os bancos de dados MEDLINE, Current Contents e EMBASE (entre 1966 e 2002) para publicações em língua inglesa utilizando as palavras-chave Homocisteína e AVC; Doença de Alzheimer; Déficit Cognitivo, Epilepsia, Depressão ou Doença de Parkinson. Artigos individuais foram pesquisados para referências cruzadas relevantes. É biologicamente plausível que altos níveis de homocisteína possam causar lesão cerebral e transtornos neuropsiquiátricos. A homocisteína é pró-aterogênica e pró-trombótica. Dessa forma, aumenta o risco de acidente vascular cerebral, podendo ter um efeito neurotóxico direto. Evidências de que a homocisteína seja um fator de risco para doença microvascular cerebral são conflitantes, mas justificam maiores estudos. Estudos transversais e alguns longitudinais suportam a crescente prevalência de acidente vascular cerebral e demência vascular em indivíduos com hiper-homocisteinemia. As evidências de crescente neurodegeneração estão se acumulando. A relação com a depressão ainda é experimental, da mesma forma como com a epilepsia. Atualmente, estudos sobre tratamentos são necessários para colocar as evidências sobre bases mais sólidas. Os pacientes de alto risco também devem ser pesquisados para hiper-homocisteínemia, cujo tratamento deve ser feito com ácido fólico. Mais evidências são necessárias antes que pesquisas populacionais possam ser recomendadas.

Humans , Homocysteine/metabolism , Hyperhomocysteinemia/psychology , Mental Disorders/etiology , Alzheimer Disease/etiology , Alzheimer Disease/metabolism , Dementia, Vascular/etiology , Dementia, Vascular/metabolism , Folic Acid/therapeutic use , Hyperhomocysteinemia/drug therapy , Hyperhomocysteinemia/metabolism , Mental Disorders/metabolism , Parkinson Disease/etiology , Parkinson Disease/metabolism , Risk Factors , Stroke/etiology , Stroke/metabolism , /therapeutic use , /therapeutic use