Association of Glial Activation and α-Synuclein Pathology in Parkinson's Disease / 神经科学通报·英文版

The accumulation of pathological α-synuclein (α-syn) in the central nervous system and the progressive loss of dopaminergic neurons in the substantia nigra pars compacta are the neuropathological features of Parkinson's disease (PD). Recently, the findings of prion-like transmission of α-syn pathology have expanded our understanding of the region-specific distribution of α-syn in PD patients. Accumulating evidence suggests that α-syn aggregates are released from neurons and endocytosed by glial cells, which contributes to the clearance of α-syn. However, the activation of glial cells by α-syn species produces pro-inflammatory factors that decrease the uptake of α-syn aggregates by glial cells and promote the transmission of α-syn between neurons, which promotes the spread of α-syn pathology. In this article, we provide an overview of current knowledge on the role of glia and α-syn pathology in PD pathogenesis, highlighting the relationships between glial responses and the spread of α-syn pathology.

Parkinson's Disease: A Multisystem Disorder / 神经科学通报·英文版

The way sporadic Parkinson's disease (PD) is perceived has undergone drastic changes in recent decades. For a long time, PD was considered a brain disease characterized by motor disturbances; however, the identification of several risk factors and the hypothesis that PD has a gastrointestinal onset have shed additional light. Today, after recognition of prodromal non-motor symptoms and the pathological processes driving their evolution, there is a greater understanding of the involvement of other organ systems. For this reason, PD is increasingly seen as a multiorgan and multisystemic pathology that arises from the interaction of susceptible genetic factors with a challenging environment during aging-related decline.

Demethylenetetrahydroberberine protects dopaminergic neurons in a mouse model of Parkinson's disease / 中国天然药物

Parkinson's disease (PD) is a multifactorial disorder of the nervous system where a progressive loss of dopaminergic neurons exist. However, the pathogenesis of PD remains undefined, which becomes the main limitation for the development of clinical PD treatment. Demethylenetetrahydroberberine (DMTHB) is a novel derivative of natural product berberine. This study was aimed to explore the neuroprotective effects and pharmacological mechanism of DMTHB on Parkinson's disease using C57BL/6 mice. A PD model of mice was induced by administration of MPTP (20 mg·kg-1) and probenecid (200 mg·kg-1) twice per week for five weeks. The mice were administered with DMTHB daily by gavage at the dose of 5 and 50 mg·kg-1 for one- week prophylactic treatment and five-week theraputic treatment. The therapeutic effects of DMTHB were evaluated by behavior tests (the open field, rotarod and pole tests), immunohistochemical staining of tyrosine hydroxylase (TH), Nissl staining and biochemical assays. The molecular mechanisms of DMTHB on the key biomarkers of PD pathological states were analyzed by Western blot (WB) and qRT-PCR. DMTHB treatment alleviated the behavioral disorder induced by MPTP-probenecid. Nissl staining and TH staining showed that the damage of dopaminergic neurons in the substantia nigra was remarkably suppressed by DMTHB treatment. Western blot results showed that the ratio of Bcl-2/Bax and TH increased, but the level of α-synuclein (α-syn) was remarkably reduced, which indicated that the apoptosis of dopaminergic neurons in mice was significantly reduced. The protein phosphorylation of p-PI3K, p-AKT and p-mTOR also increased about 2-fold, compared with the model group. Furthermore, qRT-PCR results demonstrated that the mRNA levels of pro-inflammatory cytokines, IL-1β and TNF-α, were reduced, but the level of anti-inflammatory cytokine IL-10 increased after DMTHB treatment. Finally, the cellular assay displayed that DMTHB was also a strong antioxidant to protect neuron cell line PC12 by scavenging ROS. In this study, we demonstrated DMTHB alleviates the behavioral disorder and protects dopaminergic neurons through multiple-target effects includubg anti-apoptotic, anti-inflammatory and antioxidant effects.

Neuroprotective potential of polydatin against motor abnormalities and dopaminergic neuronal loss in rotenone induced Parkinson model / Potencial neuroprotector de la polidatina contra las anomalías motoras y la pérdida neuronal dopaminérgica en un modelo de Parkinson inducido por la rotenona

Among the neurodegenerative disorders, Parkinson disease (PD) is ranked as second most common. The pathological hallmark is selective degeneration of the dopaminergic neurons in the nigro-striatal regions of brain with appearance of the Lewy bodies. Present study explores the neuro-protective potential of polydatin in terms of amelioration of degeneration of dopaminergic neurons in nigro-striatal regions of brain and distorted neuromotor behavior in the rotenone model of Parkinson's disease. Thirty-six male Sprague Dawley rats were divided into three groups. Group A (control), Group B (rotenone treated) and Group C (rotenone+polydatin treated). Rotenone was administrated intraperitoneally (i.p) at a dose of 3 mg/kg/body weight while polydatin was given i.p. at a dose of 50 mg/ kg/body weight for four weeks. Then, animals were sacrificed; substantia nigra (SN) & striatum isolated from brain and five micron thick sections were prepared. Cresyl violet (CV), H&E and Immuno-histochemical staining using anti-TH antibody was done. Motor behavior was assessed weekly throughout the experiment using five different methods. Rotenone treated parkinsonian animals showed deterioration of motor behavior, weight loss, loss of dopaminergic neurons and diminished immune-reactivity in the sections from the nigrostriatal regions of these animals Polydatin+rotenone treatment showed contradicting effects to parkinsonism, with amelioration in weight loss, neuro-motor behavior, dopaminergic loss and immune-reactivity against dopaminergic neurons. Present study revealed a neuro-protective potential of polydatin in animal model of PD by ameliorating the neuro-motor abnormalities and degeneration of dopaminergic neurons in nigrostriatal regions.

Entre los trastornos neurodegenerativos, la enfermedad de Parkinson (EP) se clasifica como la segunda más común. El sello patológico es la degeneración selectiva de las neuronas dopaminérgicas en las regiones nigro-estriatales del cerebro, con la aparición de los cuerpos de Lewy. El presente estudio explora el potencial de protección neuronal de la polidatina en términos de la mejora de la degeneración de las neuronas dopaminérgicas en las regiones nigro-estriatales del cerebro y el comportamiento neuromotor distorsionado en el modelo de rotenona de la enfermedad de Parkinson. Treinta y seis ratas macho Sprague Dawley se dividieron en tres grupos: Grupo A (control), Grupo B (tratado con rotenona) y Grupo C (tratamiento con rotenona + polidatina). La rotenona se administró por vía intraperitoneal (i.p.) a una dosis de 3 mg/kg/peso corporal, mientras que la polidatina se administró i.p. a una dosis de 50 mg/kg/ peso corporal durante cuatro semanas. Posteriormente, los animales fueron sacrificados. Se aislaron la substantia nigra (SN) y cuerpo estriado de los cerebros y se realizaron secciones de cinco micras de espesor. Se realizó una tinción de violeta de cresilo (CV), H&E y tinción inmunohistoquímica usando anticuerpo anti-TH. El comportamiento motriz se evaluó semanalmente durante todo el experimento utilizando cinco métodos diferentes. Los animales parkinsonianos tratados con rotenona mostraron deterioro del comportamiento motriz, pérdida de peso, pérdida de neuronas dopaminérgicas y disminución de la reactividad inmune en las secciones de las regiones nigroestriadas. El tratamiento con polidatina + rotenona mostró efectos contrarios al parkinsonismo, con mejoría en la pérdida de peso, en el comportamiento motor, en la pérdida dopaminérgica y en la reactividad inmune contra las neuronas dopaminérgicas. El presente estudio reveló un potencial de protección neuronal de la polidatina en el modelo animal de la EP al mejorar las anomalías neuro-motoras y la degeneración de las neuronas dopaminérgicas en las regiones nigroestriatales.

Does Parkinson's disease start in the gut? / A doença de Parkinson começa no intestino?

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.

Actualización en enfermedad con cuerpos de Lewy / Update in Lewy body disease

La enfermedad con cuerpos de Lewy incluye 2 entidades que podrían ser consideradas variantes clínicas de una misma patología: la demencia con cuerpos de Lewy y la demencia en enfermedad de Parkinson. Con la finalidad de describir correctamente lo que sucede en la evolución de la enfermedad se divide el cuadro en etapa prodrómica y de demencia propiamente dicha. La primera está clínicamente representada por aquel período en el cual, si bien el paciente exhibe algunos signos y síntomas propios de la enfermedad, no reúne criterios de demencia. A pesar de ser difícil de definir y por carecerse todavía de contundentes datos clínicos y biomarcadores, se caracteriza principalmente por deterioro leve selectivo en función atencional ­ visuoespacial, trastorno del sueño REM y disautonomía‒. La segunda etapa está claramente caracterizada en los criterios de consenso del año 2005. Recientemente hemos publicado la validación de un instrumento llamado ALBA Screening Instrument, que permite diagnosticar con alta sensibilidad y especificidad la enfermedad aun en etapas tempranas y diferenciarla de otras patologías semejantes. La tomografía por emisión de positrones (PET) para transportador de dopamina es el procedimiento de referencia (gold standard) del diagnóstico. El tratamiento sintomático con anticolinesterásicos y neurolépticos atípicos favorece una buena evolución de la enfermedad y es fundamental tener en cuenta evitar medicamentos que pueden dañar gravemente a los pacientes como los anticolinérgicos y antipsicóticos típicos. Los avances en el diagnóstico y la difusión del impacto de esta enfermedad en la población contribuirán a generar mayores esfuerzos de investigación para hallar un tratamiento eficaz, preventivo o curativo o de ambas características. (AU)

Lewy body disease includes 2 entities that could be considered clinical variants of the same pathology: Dementia with Lewy bodies and Parkinson's disease Dementia. Two stages of the disease are described in this review, a prodromal stage and one of explicit dementia. The first one is clinically represented by that period in which, the patient exhibits some typical features of the disease, but not dementia criteria. Despite being difficult to define the prodromal stage and that strong clinical data and biomarkers are still lacking, there is evidence to characterize it mainly by mild selective impairment in attention and visuo-spatial function, REM sleep disorder and dysautonomia. The second stage is clearly characterized in the known consensus criteria of 2005. We have recently published the validation of an instrument called ALBA Screening Instrument which showed a high sensitivity and specificity for diagnosis of the disease even in the early stages. It´s useful to differentiate the disease from other similar pathologies. Positron Emission Tomography for dopamine transporter is the gold standard of diagnosis in life. Symptomatic treatment with anticholinesterases and atypical neuroleptics help patients in their evolution of the disease. Anticholinergics and typical antipsychotics are agents to avoid in the treatmen of the disease because can severely damage patients. Future advances in the diagnosis and dissemination of the knowledge of the disease will contribute to generate greater research efforts to find an effective preventive and / or curative treatment. (AU)

Efeito do 8-metoxipsoraleno(8-mop)na citotoxicidade da retonona sobre células do sistema nervoso central, um modelo de doença de parkinson in vitro / Effect of 8-methoxypsoralen (8-MOP) on the cytotoxicity of rotenone on the central nervous system cells, a model of Parkinson's disease in vitro

Doença de Parkinson (DP) é caracterizada por uma perda seletiva e profunda dos neurônios dopaminérgicos da substância nigra pars compacta (SNpc) do mesencéfalo, acompanhada pela espoliação de dopamina no corpo estriado. A maioria dos casos de DP apresenta etiologia multifatorial, com a presença de componentes genéticos e ambientais. Embora existam diferentes causas possíveis, a patogênese da desordem parece convergir para mecanismos relacionados à disfunção mitocondrial, estresse oxidativo e mau enovelamento proteico. Um modelo estabelecido na literatura para estudo desta doença, tanto in vitro quanto in vivo é a administração de rotenona, um pesticida derivado de plantas que inibe o complexo I mitocondrial e favorece a geração de espécies reativas de oxigênio (ERO), levando a uma espoliação de glutation reduzido (GSH) através do processo de detoxificação destes compostos eletrofílicos, catalisados por glutation S-transferases (GSTs). Sendo assim, a busca por novas substâncias com atividade neuroprotetora é atualmente o foco de estudos, e metabólitos isolados de plantas podem ser fontes destas moléculas. Dessa forma, o 8-metoxipsoraleno (8-MOP), uma furocumarina, foi testado como um possível agente protetor sobre a citotoxicidade causada pela rotenona em modelos in vitro de gliomas, considerando o papel do glutation neste processo. O estudo adotou uma abordagem que associa técnicas bioquímicas e de biologia celular. Ensaios de viabilidade celular foram realizados em células de glioma murino (C6) e glioblastoma multiforme humano (U251) através da redução do brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium (MTT)...

Parkinson’s disease (PD) is characterized by a profound and selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) accompanied by midbrain dopamine depletion in the striatum. Most cases of PD present multifactorial etiologies, with the presence of genetic and environmental components. Although there are different possible causes, the pathogenesis of the disorder seems to converge to mechanisms related to mitochondrial dysfunction, oxidative stress and bad protein folding. An established model in the literature to study this disease, both in vitro and in vivo is rotenone administration, a pesticide derived from plants that inhibits the mitochondrial complex I and favors the generation of reactive oxygen species (ROS), leading to reduced glutathione (GSH) depletion through the detoxification process of this electrophilic compound catalyzed by glutathione S-transferases (GSTs). Thus, the search for new substances with neuroprotective activity is currently the focus of studies, and plant isolated metabolites can be sources of these molecules. Thus, 8-methoxypsoralen (8-MOP), a furocoumarin, was tested as a potential protective agent on the cytotoxicity caused by rotenone in glioma cells in vitro models, considering the role of glutathione in the process. The study adopted an approach that combines biochemical and cell biology techniques. Cell viability assays were performed in murine glioma cells (C6) and human glioblastoma (U251) cells through the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)...

Clinical profile of Parkinson's disease in the Gumei community of Minhang district, Shanghai

OBJECTIVE: We examined the demographic and clinical profiles of Parkinson's disease in Shanghai, China, to assist in disease management and provide comparative data on Parkinson's disease prevalence, phenotype, and progression among different regions and ethnic groups. METHODS: A door-to-door survey and follow-up clinical examinations identified 180 community-dwelling Han-Chinese Parkinson's disease patients (104 males, 76 females). RESULTS: The average age at onset was 65.16±9.60 years. The most common initial symptom was tremor (112 patients, 62.22%), followed by rigidity (38, 21.11%), bradykinesia (28, 15.56%) and tremor plus rigidity (2, 1.11%). Tremor as the initial symptom usually began in a single limb (83.04% of patients). The average duration from onset to mild Parkinson's disease (Hoehn-Yahr phase 1-2) was 52.74±45.64 months. Progression from mild to moderate/severe Parkinson's disease (phase≥3) was significantly slower (87.07±58.72 months; p<0.001), except for patients presenting initially with bradykinesia (53.83±24.49 months). Most patients (149/180, 82.78%) took levodopa with or without other drugs. The Hamilton Anxiety Scale revealed symptoms of clinical anxiety in 35 patients, and the Hamilton Depression Scale revealed depressive symptoms in 88 patients. The depressed or anxious subgroup (123 patients) demonstrated a significantly younger age at onset (55.54±7.68 years) compared with the overall mean (p<0.05). CONCLUSION: Unilateral limb tremor was the most common initial symptom, and motor function deteriorated slowly over ≅4−9 years. Earlier-onset patients experience greater psychiatric dysfunction. .

Studying neurodegenerative diseases in culture models

Neurodegenerative diseases are pathological conditions that have an insidious onset and chronic progression. Different models have been established to study these diseases in order to understand their underlying mechanisms and to investigate new therapeutic strategies. Although various in vivo models are currently in use, in vitro models might provide important insights about the pathogenesis of these disorders and represent an interesting approach for the screening of potential pharmacological agents. In the present review, we discuss various in vitro and ex vivo models of neurodegenerative disorders in mammalian cells and tissues.

Animal models of neurodegenerative diseases

The prevalence of neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), increases with age, and the number of affected patients is expected to increase worldwide in the next decades. Accurately understanding the etiopathogenic mechanisms of these diseases is a crucial step for developing disease-modifying drugs able to preclude their emergence or at least slow their progression. Animal models contribute to increase the knowledge on the pathophysiology of neurodegenerative diseases. These models reproduce different aspects of a given disease, as well as the histopathological lesions and its main symptoms. The purpose of this review is to present the main animal models for AD, PD, and Huntington's disease.

Síntomas no motores en pacientes con enfermedad de parkinson. Hospital de San José, Bogotá, DC Colombia / Non-motor symptoms in parkinson disease patients Hospital de San José, Bogotá DC. Colombia

La enfermedad de Parkinson (EP) es la segunda afección neurodegenerativa en frecuencia con una prevalencia en Colombia de 4.7 por mil habitantes. Los síntomas no motores (SNM) hacen parte del espectro ya que generan un aumento de la morbilidad e impactan la calidad de vida. Objetivo general: describir la frecuencia de SNM en pacientes con EP que asisten a la consulta externa de neurología en el Hospital de San José de Bogotá DC. Métodos: serie de adultos que consultaron entre abril y septiembre de 2011 cumpliendo criterios diagnósticos de EP según UK Brain Data Bank. Se utilizó el cuestionario de SNM para EP, PD NMS quest, validado en español. Resultados: se encuestaron 55 pacientes con edad promedio de 68 años (DE 9.8), hombres 61.8%. El 51%, con un tiempo de evolución menor o igual a cinco años. El 85.5% tenían una puntuación en escala de Hoehn y Yahr entre I-II. Los SNM más frecuentes son urgencia urinaria 76.4%, tristeza 74.5%, sensación desagradable en las piernas durante la noche o necesidad de moverlas 67.2% y problemas para recordar cosas 61.8%. Conclusiones: los SNM son frecuentes en nuestra población siendo el sistema urinario es el más comprometido. Se debe indagar sobre estos para brindar un manejo integral al paciente. Se requieren más estudios en nuestra población que evalúen el impacto sobre la calidad de vida.

Parkinson´s disease (PD) is the second most common neurodegenerative disorder with a prevalence of 4.7 per 1000 people in Colombia. Non-motor symptoms (NMS) are included in the spectrum for they lead to increased morbility and impaired quality of life. Overall Objective: to describe the frequency of NMS in patients diagnosed with PD who attend the neurology outpatient clinic at Hospital de San José de Bogotá DC. Methods: series of adults who consulted between April and September 2011 who met the diagnostic criteria for PD according to the UK Brain Data Bank. The PD NMS quest questionnaire validated in Spanish was used. Results: fifty-five patients, men 61.8%, average age 68 years (SD 9.8) were surveyed. A clinical course equal to or less than 5 years was documented in 51% Repert.med.

Relação entre a doença de Parkinson e o gene LRRK2: um estudo na população brasileira / Relationship between Parkinson's disease and gene LRRK2: a study in brazilian population

A doença de Parkinson (DP) é a segunda doença neurodegenerativa mais frequente depois da Doença de Alzheimer, afetando aproximadamente 1% da população com idade superior a 65 anos. Clinicamente, esta doença caracteriza-se pela presença de tremor em repouso, bradicinesia, rigidez muscular e instabilidade postural, os quais podem ser controlados com a administração de levodopa. As características patológicas da DP incluem a despigmentação da substãncia nigra devido à perda dos neurônios dopaminérgicos e a presença de inclusões proteicas denominadas corpos de Lewy nos neurônios sobreviventes. As vias moleculares envolvidas com esta patologia ainda são obscuras, porém a DP é uma doença complexa, resultante da interação entre fatores ambientais e causas genéticas. Mutações no gene leucine-rich repeat kinase 2 (LRRK2; OMIM 609007) constituem a forma mais comum de DP. Este gene codifica uma proteína, membro da família de proteínas ROCO, que possui, entre outros domínios, dois domínios funcionais GTPase (ROC) e quinase (MAPKKK). Neste estudo, os principais domínios do gene LRRK2 foram analisados em 204 pacientes brasileiros com DP por meio de sequenciamento dos produtos da PCR. Através da análise de 14 exons correspondentes aos domínios ROC, COR e MAPKKK foram identificadas 31 variantes. As alterações novas, p.C1770R E p.C2139S, possuem um potencial papel na etiologia da DP. Três alterações exônicas (p.R1398R, p.T1410M e p.Y2189C) e nove intrônicas (c.4317+16C>T, c.5317+59A>C, c.5509+20A>C, c.5509+52T>C, c.5509+122A>G, c.5657-46C>T, c.6382-36G>A, c.6382-37C>T e c.6576+44T>C) são potencialmente não patogênicas. Ao todo, dezessete variantes exônicas e intrônicas constituem polimorfismos já relatados na literatura (p.R1398H, p.K1423K, p.R1514Q, p.P1542S, c.4828-31T>C, p.G1624G, p.K1637K, p.M1646T, p.S1647T, c.5015+32A>G, c.5170+23T>A, c.5317+32C>T, p.G1819G, c.5948+48C>T, p.N2081D, p.E2108E e c.6381+30A>G). A frequência total de alterações potencialmente patogênicas...

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, affecting nearly 1% of people above 65 years of age. The major clinical symptoms of this disease are: resting tremor, bradykinesia, rigidity, postural instability and a positive response to dopamine replacement therapy. Pathological findings include selective degeneration of dopaminergic neurons within the substantia nigra, with proteinaceous Lewy body inclusions in surviving cells. The pathogenesis of PD is not yet completely understood, however, both genetic and environmental factors contribute to the disease phenotype. Mutations in the leucine-rich repeat kinase 2 gene (LRRK2; OMIM 609007) represent the most frequent genetic known cause of familial and sporadic PD. The LRRK2 gene encodes a protein, member of the ROCO protein family, that contains both GTPase (ROC) domain and kinase (MAPKKK) domain, as well as, other motifs. In this study, we have screened the main domains of the LRRK2 in a group of 204 PD Brazilian patients. The screening was performed by direct sequencing of the PCR products. By the analysis of 14 exons corresponding to ROC, COR and MAPKKK domains, we identified 31 sequence variations. The novel variants, p.C1770R and p.C2139S, may play a role in the PD pathogenesis. Three exonic altetations (p.R1398R, p.T1410M and p.Y2189C) and nine intronic variants (c.4317+16C>T, c.5317+59A>C, c.5509+20A>C, c.5509+52T>C, c.5509+122A>G, c.5657-46C>T, c.6382-36G>A, c.6382-37C>T and c.6576+44T>C) seem to be not pathogenic. A total of 17 exonic and intronic alterations were previously described in the literature as non-pathogenic polymorphisms (p.R1398H, p.K1423K, p.R1514Q, p.P1542S, c.4828-31T>C, p.G1624G, p.K1637K, p.M1646T, p.S1647T, c.5015+32A>G, c.5170+23T>A, c.5317+32C>T, p.G1819G, c.5948+48C>T, p.N2081D, p.E2108E and c.6381+30A>G). The frequency of pathogenic mutations or potentially pathogenic variants was 3.4% (including the p.G2019S mutation...

Morphometry MRI in the differential diagnosis of parkinsonian syndromes / Morfometria por ressonância magnética no diagnóstico diferencial das síndromes parkinsonianas

This study evaluates the diagnostic value of morphometric magnetic resonance imaging (MRI) in the differential diagnosis among Parkinson's disease (PD), progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). We studied 21 PD cases, 11 MSA-c, 8 MSA-p and 20 PSP cases. Midbrain area (Ams), pons area (Apn), middle cerebellar peduncle (MCP) and superior cerebellar peduncle (SCP) were measured using MRI. Comparisons were made between PD, MSA-p, MSA-c and PSP. Apn, MCP and SCP morphometry dimensions presented differences among groups. Ams below 105 mm² and SCP smaller than 3 mmwere the most predictive measures of PSP (sensitivity 95.0 and 80.0 percent, respectively). For the group of MSA-c patients, Apn area below 315 mm² showed good specificity and positive predictive value (93.8 percent and 72.7 percent, respectively). In conclusion, dimensions and cut off values obtained from routine MRI can differentiate between PD, PSP and MSA-c with good sensitivity, specificity and accuracy.

Morfometria pela ressonância magnética (RM) no diagnóstico diferencial entre doença de Parkinson (DP), paralisia supranuclear progressiva (PSP) e atrofia de múltiplos sistemas (AMS). Este estudo avaliou a RM no diagnóstico diferencial de 21 casos com DP, 11 AMS-c, 8 AMS-p e 20 com PSP. A área sagital do mesencéfalo (Ams), área sagital da ponte (Apn), largura do pedúnculo cerebelar médio (PCM) e pedúnculo cerebelar superior (PCS) foram medidas pela RM e realizadas comparações entre destes pacientes. A Ams <105 mm² e a largura média do PCS <3 mm foram preditivas para PSP (sensibilidade de 95,0 e 80,0 por cento, respectivamente). Nos casos de AMS-c a área pontina <315 mm² apresentou boa especificidade e valor preditivo positivo para o diagnóstico (93,8 por cento e 72,7 por cento). Em conclusão, as dimensões e valores de cortes obtidos a partir da RM podem diferenciar PD, PSP e AMS-c, com sensibilidade, especificidade e precisão.

Frequency of FMR1 premutation in individuals with ataxia and/or tremor and/or parkinsonism

A late onset neurological syndrome in carriers of premutation in FMR1 gene was recently described. The condition was named fragile-X-associated tremor/ataxia syndrome (FXTAS) and includes intentional tremor, cerebellar ataxia, parkinsonism, and cognitive deficit. We ascertained the contribution of FMR1 premutation to the phenotypes ataxia, tremor and/or parkinsonism. Sixty-six men over 45 years old presenting these symptoms, isolated or combined, were tested. Also, 74 normal men, randomly chosen in the population, formed the control group. In the patient group, no premutation carrier was found, which is in agreement with other observed frequencies reported elsewhere (0-5% variation). No significant differences were found when comparing gray zone allele frequencies among target and control groups. The FXTAS contribution in patients with phenotypic manifestations of FXTAS was 15/748 (2%). The presence of gray zone alleles is not correlated with FXTAS occurrence.

Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's disease

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.

Declínio cognitivo e demência associados à doença de Parkinson: características clínicas e tratamento / Cognitive impairment and dementia in Parkinson's disease: clinical characteristics and treatment

CONTEXTO: A doença de Parkinson (DP) é uma moléstia progressiva de causa desconhecida, com características motoras que incluem tremor de repouso, rigidez, bradicinesia e alterações posturais. Mas o comprometimento cognitivo é comum mesmo nos indivíduos não dementes. Somando-se a isso, a DP associa-se a um aumento de risco de desenvolver demência. OBJETIVOS: Esta revisão analisa a perda cognitiva associada à DP, sobre seus aspectos, fatores de risco, fisiopatologia e tratamento. MÉTODOS: Esta revisão incorporou artigos obtidos pelo Medline. RESULTADOS: Pacientes com DP, com ou sem demência, têm desempenho reduzido em vários testes cognitivos. Essa redução cognitiva pode ser atribuída à disfunção dos circuitos conectores da região frontal aos núcleos da base. Distúrbio cognitivo leve pode progredir para demência em certos pacientes. Identificaram-se alguns fatores de risco para o desenvolvimento de demência e revelaram-se aspectos sobre a fisiopatologia. CONCLUSÃO: As características neuropsicológicas da DP, as quais refletem predominantemente disfunção frontal, podem ser atribuídas a anormalidades do circuito fronto-estriatal. Mas a fisiopatologia responsável pela demência associada à DP não está completamente compreendida. Anticolinesterásicos e memantina têm um modesto efeito contra sintomas cognitivos. Detecção precoce dos fatores de risco para o desenvolvimento de demência pode ajudar a criar estratégias preventivas.

BACKGROUND: Parkinson disease (PD) is a progressive illness of undetermined cause with characteristic motor findings that include rest tremor, rigidity, bradykinesia, and postural disturbance. But cognitive impairment is common even in nondemented. In addition PD has been associated with an increased risk of developing dementia. OBJECTIVES: This review provides an analysis of the cognitive impairment associated with PD, about its aspects, risk factors, pathophysiology, and treatment. METHODS: The current review incorporates articles obtained through Medline. RESULTS: Non-demented and demented patients with Parkinson's disease are impaired in several cognitive tasks. These impairments may be attributed to dysfunction the circuits connecting the frontal cortical regions and the basal ganglia. Mild cognitive dysfunctions may progress to dementia in some patients. Some risk factors for the development of dementia were identified and aspects of pathophysiology were disclosed. CONCLUSION: Neuropsychological profile of PD, which predominantly reflects frontal dysfunction, may be attributed to disruption of the frontoestriatal circuitry. But the pathophysiology underlying dementia in PD is not completely understood. Cholinesterase inhibitors and memantine have a modest effect against cognitive symptoms. Early detection of risk factors for development of dementia may help to create preventive strategies.