Coumarin analogue 3-methyl-7H-furo[3,2-g]chromen-7-one as a possible antiparkinsonian agent / El análogo de cumarina 3-metil-7H-furo[3,2-g]cromen-7-ona, un posible agente antiparkinsoniano

Abstract Introduction: Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B. Objective: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity. Materials and methods: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively. Results: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity. Conclusion: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.

Resumen Introducción. El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B. Objetivo. Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo [3,2-g ] chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante. Materiales y métodos. Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005. Resultados. El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes. Conclusión. Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.

Electroacupuncture Alleviates Motor Symptoms and Up-Regulates Vesicular Glutamatergic Transporter 1 Expression in the Subthalamic Nucleus in a Unilateral 6-Hydroxydopamine-Lesioned Hemi-Parkinsonian Rat Model / 神经科学通报·英文版

Previous studies have shown that electroacupuncture (EA) promotes recovery of motor function in Parkinson's disease (PD). However the mechanisms are not completely understood. Clinically, the subthalamic nucleus (STN) is a critical target for deep brain stimulation treatment of PD, and vesicular glutamate transporter 1 (VGluT1) plays an important role in the modulation of glutamate in the STN derived from the cortex. In this study, a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD was treated with 100 Hz EA for 4 weeks. Immunohistochemical analysis of tyrosine hydroxylase (TH) showed that EA treatment had no effect on TH expression in the ipsilateral striatum or substantia nigra pars compacta, though it alleviated several of the parkinsonian motor symptoms. Compared with the hemi-parkinsonian rats without EA treatment, the 100 Hz EA treatment significantly decreased apomorphine-induced rotation and increased the latency in the Rotarod test. Notably, the EA treatment reversed the 6-OHDA-induced down-regulation of VGluT1 in the STN. The results demonstrated that EA alleviated motor symptoms and up-regulated VGluT1 in the ipsilateral STN of hemi-parkinsonian rats, suggesting that up-regulation of VGluT1 in the STN may be related to the effects of EA on parkinsonian motor symptoms via restoration of function in the cortico-STN pathway.

Deep brain stimulation in Parkinson's disease: analysis of the variation in final stimulating lead placement based on multi-tract electrode recordings

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (SNT) is a treatment modality for Parkinson's Disease (PD). Either single central trajectory tract or multiple selected trajectory tracts based on microelectrode recordings (MER) are used for the placement of the final stimulating electrodes. This study aims to explore how many times trajectory tracts, other than the central tract are used for final lead placement.Methods: Retrospective analysis of a randomly selected convenience sample of 24 subjects from patients who had DBS by a single neurosurgeon. After MRI and CT assessment, planning using a stereotactic frame for variable trajectory placement of temporary electrodes and MER that was the basis for site and tract selection for the final electrode placements used for DBS. Results: Twenty four patients had 47 DBS electrodes placed: 1 unilateral and 23 bilateral. The central tract was used in 45 (95.75%) of these cases. The central trajectory tract accounted for 30 (63.83%), the anterior trajectory tract for 7 (14.89%), the medial tract for 5 (10.64%), the posterior for 4 (8.51%) and the lateral for 1 (2.13%) of final lead placements. Conclusion: The results of this study based on the predicted best stimulating sites following MER show that alternates to the central trajectory tract are required in 37% of site placements. A comparative study exploring clinical benefit is required to assess if variable electrode trajectory placement based on accurate physiological measurements is superior to single central trajectory placement

Effect of adenosine A2A receptor antagonists on motor disorders induced by 6-hydroxydopamine in rat

PURPOSE: To investigate the role of adenosine A2A receptors on 6-OHDA-induced motor disorder in rat. METHODS: In order to induce experimental model of Parkinson's disease, 6-hydoxydopamine (8 μg/rat) was injected unilaterally into the SNc. After three weeks as a recovery period, 6-OHDA-induced bradykinesia and balance disturbances were assessed by using beam traversal test 10, 30 and 60 minutes after intraperitoneal injections of the drugs (caffeine, SCH58261). RESULTS: The results showed that 6-OHDA (8 μg/rat, Intra-SNc) induced motor disorders of Parkinson's disease and increased elapsed time in the beam test (p<0.001). Injection of caffeine (30 mg/kg, i.p.) and SCH58261 (2 mg/kg, i.p.) attenuated elapsed time on beam (p<0.01 and p<0.001). We showed that acute administration of caffeine and SCH 58261 can improve the 6-OHDA-induced bradykinesia and motor disturbance. CONCLUSION: Adenosine A2AR antagonists improve 6-OHDA-motor deficit and this effect seems to be mediated by the inhibition of A2A presynaptic receptors in substantia nigra pars compacta.

Fat gain with physical detraining is correlated with increased glucose transport and oxidation in periepididymal white adipose tissue in rats

As it is a common observation that obesity tends to occur after discontinuation of exercise, we investigated how white adipocytes isolated from the periepididymal fat of animals with interrupted physical training transport and oxidize glucose, and whether these adaptations support the weight regain seen after 4 weeks of physical detraining. Male Wistar rats (45 days old, weighing 200 g) were divided into two groups (n=10): group D (detrained), trained for 8 weeks and detrained for 4 weeks; and group S (sedentary). The physical exercise was carried out on a treadmill for 60 min/day, 5 days/week for 8 weeks, at 50-60% of the maximum running capacity. After the training protocol, adipocytes isolated from the periepididymal adipose tissue were submitted to glucose uptake and oxidation tests. Adipocytes from detrained animals increased their glucose uptake capacity by 18.5% compared with those from sedentary animals (P<0.05). The same cells also showed a greater glucose oxidation capacity in response to insulin stimulation (34.55%) compared with those from the S group (P<0.05). We hypothesize that, owing to the more intense glucose entrance into adipose cells from detrained rats, more substrate became available for triacylglycerol synthesis. Furthermore, this increased glucose oxidation rate allowed an increase in energy supply for triacylglycerol synthesis. Thus, physical detraining might play a role as a possible obesogenic factor for increasing glucose uptake and oxidation by adipocytes.

Cognitive Dysfunction in Drug-induced Parkinsonism Caused by Prokinetics and Antiemetics

The use of prokinetics/antiemetics is one of the leading causes of drug-induced parkinsonism (DIP) observed in neurology clinics. Cognitive dysfunction in DIP has recently been recognized, but pathologies related with cognitive dysfunction is unknown. Among our retrospective cohort of 385 consecutive parkinsonian patients enrolled in our parkinsonism registry, 14 patients were identified who satisfied our inclusion criteria: parkinsonism caused by prokinetics/antiemetics, existing T1-weighted 3D volumetric MR images, and normal [18F]-N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane PET scan images. For the comparison of volumetric MR data, 30 age- and sex-matched healthy individuals were included in this study. Among 14 patients with DIP, 4 patients were diagnosed with dementia, and all other patients had mild cognitive impairment (MCI). Comparisons of MR volumetric data between DIP patients with MCI and controls show that cortical gray matter volumes are reduced bilaterally in DIP (P=0.041) without changes in either total white matter volume or total intracranial volume. Among subcortical structures, the volume of the right hippocampus is reduced in DIP patients compared with controls (P=0.011, uncorrected). In DIP, cortical thickness is reduced in the bilateral lingual (P=0.002), right fusiform (P=0.032) and part of the left lateral occipital gyri (P=0.007). Our results suggests that cognitive dysfunction in DIP caused by prokinetics/antiemetics is common. Structural changes in the brain by 3D MRI may be associated with cognitive decline in DIP.

Common Complications after Hypoxic-ischemic Encephalopathy

Hypoxic-ischemic encephalopathy (HIE) is one of the major disease for neuro-rehabilitation, as well as one of the important impairment. HIE typically shows global deterioration of brain function with relative preservation of brain stem reflexes, and topographic pattern of damage; the CA1 hippocampal cells, cerebellar Purkinje cells, neocortical neurons in layers 3, 5, 6 and basal ganglia. The characteristics of patho-mechanism including persistent vegetative state, seizure, autonomic dysfunction and secondary Parkinsonism are causative factors of several complications. Management of these complications sometimes curative, but more often re-adaptive and palliative. Understanding and proper rehabilitation of complications will be one of the most important therapeutic strategies for patients with HIE.

Protective effect of alkaloids from Piper longum in rat dopaminergic neuron injury of 6-OHDA-induced Parkinson's disease / 中国中药杂志

<p><b>OBJECTIVE</b>To discuss the protective effect of alkaloids from Piper longum (PLA) in rat dopaminergic neuron injury of 6-OHDA-induced Parkinson's disease and its possible mechanism.</p><p><b>METHOD</b>The rat PD model was established by injecting 6-OHDA into the unilateral striatum with a brain solid positioner. The PD rats were divided into the PLA group (50 mg x kg(-1) x d(-1)), the madorpa group (50 mg x kg(-1) x d(-1)) and the model group, with 15 rats in each group. All of the rats were orally given drugs once a day for 6 weeks. Meanwhile, other 15 rats were randomly selected as the sham operation group, and only injected with normal saline in the unilateral striatum. The behavioral changes were observed with the apomorphine (APO)-induced rotation and rotary rod tests. The number of tyrosine hydroxylase (TH)-positive cells in rat substantia nigra and the density of TH-positive fibers in striatum were detected by tyrosine hydroxylase immunohistochemistry. The content of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione (GSH), catalase (CAT), malondialdehyde (MDA), nitric oxide (NO) and nitric oxide synthase (NOS) in rat substantia nigra and striatum were measured by the spectrophotometric method.</p><p><b>RESULT</b>After being induced by APO, PD rats showed obvious rotation behaviors, with decreased time stay on rotary rod and significant reduction in the number of TH-positive cells in sustantia nigra and the density of TH-positive fibers in striatum. The activities of SOD, GSH-Px, CAT, the content of GSH and the total antioxidant capacity significantly decreased, whereas the activities of NOS and the content of MDA, NO significantly increased. PLA could significantly improve the behavioral abnormality of PD rats and increase the number of TH-positive cells in sustantia nigra and the density of TH-positive fibers in striatum. It could up-regulate the activities of SOD, GSH-Px, CAT, the content of GSH and the total antioxidant capacity, and decrease the content of NOS and the content of MDA, NO.</p><p><b>CONCLUSION</b>Alkaloids from P. longum shows the protective effect in substantia nigra cells of 6-OHDA-induced PD model rats. Its mechanism may be related with their antioxidant activity.</p>

Vascular parkinsonism: a case series of 17 patients / Parkinsonismo vascular: uma serie de casos de 17 pacientes

Objective To report the clinical and neuroimaging findings in a case series of vascular parkinsonism (VP). Methods Seventeen patients with VP were evaluated with motor, cognitive, and neuroimaging standardized tests and scales. Results All patients had arterial hypertension. Ten patients were male and the mean age of the whole sample was 75.8±10.1 years. The mean age of parkinsonism onset was 72.2±10.0 years. Common clinical features were urinary incontinence (88.2%), lower limb parkinsonism with freezing of gait and falls (82.3%), and pyramidal signs (76.4%). The mean Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn-Yahr scores were 72.5±21.6 points and 3.3±0.9 points, respectively. Sixteen (94.1%) patients had freezing of gait and executive dysfunction. Twelve (70.5%) patients had probable vascular dementia. The mean dose of levodopa was 530.9 mg/day. Unresponsiveness to the drug was confirmed by a 6.9 mean point reduction in the UPDRS score after the “practically defined off” test. Conclusion This series provides a profile of VP with predominant lower-limb involvement, freezing of gait and falls, pyramidal signs, executive dysfunction, concomitant vascular dementia, and poor levodopa response. .

Objetivo Relatar os achados clínicos e de neuroimagem em parkinsonismo vascular (PV). Métodos Foram avaliados 17 pacientes com PV do ponto de vista motor, cognitivo e de neuroimagem através de testes e escalas padronizados. Resultados Dos 17 pacientes, 10 (58,5%) eram homens; a média de idade média foi 75,8±10,1 anos. Todos os pacientes eram hipertensos; a média de idade do início do parkinsonismo foi 72,2±10,0 anos. Achados clínicos mais frequentes: incontinência urinária (88,2%); parkinsonismo de membros inferiores com bloqueio de marcha e quedas (82,3%); sinais piramidais (76,4%). A média dos escores UPDRS e Hoehn-Yahr foram, respectivamente, 72,5±21,6 e 3,3±0,9 pontos. Dezesseis pacientes (94,1%) apresentaram bloqueio de marcha e disfunção executiva. Doze pacientes (70,5%) preencheram critérios para demência vascular provável. A dose média de levodopa foi 530,9 mg/dia e os pacientes tiveram uma baixa resposta à droga, tendo havido redução de apenas 6,9 pontos em média no escore UPDRS após o teste “practically-defined off”. Conclusão O perfil de PV encontrado neste estudo foi caracterizado por: envolvimento predominante de membros inferiores, com bloqueio de marcha e quedas; sinais piramidais; disfunção executiva; demência vascular concomitante e resposta pobre à levodopa. .

Exposure to pesticides and heterozygote genotype of GSTP1-Alw26I are associated to Parkinson's disease / Exposição a pesticidas e genótipo heterozigoto de GSTP1-Alw26I associam-se à doença de Parkinson

Objective This study aimed to analyze the frequency of GSTP1-Alw26I polymorphism and to estimate its association with toxic substances in Parkinson's disease (PD). Methods A study group with 154 patients - subdivided into familial and sporadic PD groups - and 158 elderly individuals without the disease (control group) were evaluated. GSTP1-Alw26I polymorphism was analyzed by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Results Patients were significantly more exposed to pesticides compared with the control group (p=0.0004), and the heterozygote genotype associated to exposure to pesticides also prevailed in patients (p=0.0001). Wild homozygote genotype was related to tobacco use (p=0.043) and alcoholism (p=0.033) in familial PD patients. Conclusion Exposure to pesticides is associated to PD, whose effect can be enhanced when combined with the heterozygote genotype of GSTP1-Alw26I. Also, large genetic and environmental studies considering tobacco use, alcoholism, GSTP1 and PD are necessary to confirm our findings. .

Objetivo Analisar a frequência do polimorfismo GSTP1-Alw26I, assim como estimar sua associação com substâncias tóxicas na doença de Parkinson (DP). Métodos A casuística avaliada foi composta por um grupo de estudo, com 154 pacientes, subdivididos em DP familial e esporádica, e outro com 158 idosos sem a doença (grupo controle). O polimorfismo GSTP1-Alw26I foi analisado por reação em cadeia da polimerase/polimorfismo de comprimento do fragmento de restrição (PCR/RFLP). Resultados Os pacientes foram significativamente mais expostos a pesticidas, comparados com o grupo controle (p=0,0004), e o genótipo heterozigoto associado a exposição a pesticidas também prevaleceu nos pacientes (p=0,0001). O genótipo homozigoto selvagem apresentou relação com tabagismo (p=0,043) e etilismo (p=0,033) em pacientes com DP familial. Desse modo, a exposição a pesticidas está associada à DP, cujo efeito pode ser potencializado quando combinado ao genótipo heterozigoto de GSTP1-Alw26I. Estudos genético-ambientais envolvendo tabagismo, etilismo, GSTP1 e DP devem ser realizados em casuísticas numerosas, confirmando essa associação. .

Parkinsonismo induzido por trazodona durante o tratamento de hérnia discal lombar: relato de caso / Trazodone induced parkinsonism during lumbar disc herniation treatment: case report

A utilização de medicações psicoativas vem crescendo ao longo dos anos, sendo essencial o conhecimento de seus efeitos colaterais e interações medicamentosas. O desenvolvimento de distúrbios de movimento associados ao uso dessas substâncias é uma situação bastante desconfortável para o paciente, sendo essencial o diagnóstico adequado mediante forte suspeição. Relata-se o caso de um paciente que desenvolveu sintomas de parkinsonismo durante tratamento de hérnia discal lombar na vigência do uso de trazodona. É dada ênfase aos mecanismos de produção desse fenômeno e à sua condução clínica...

The use of psychoactive medications has been growing over years, being essential the knowledge of its side effects and interactions. The development of movement disturbances is a very uncomfortable situation for the patient, requiring a high suspicion for adequate diagnosis. A case of a patient who presented symptoms of Parkinsonism during use of Trazodone in the treatment of lumbar disc herniation is reported. Emphasis is given to the biological mechanisms of this phenomenon and its clinical conduction...

Neurotoxicity and biomarkers of lead exposure: a review / 中国医学科学杂志(英文版)

Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes, public health decision making, and primary prevention synthesis. Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies. Biomarkers are generally classified into three groups: biomarkers of exposure, effect, and susceptibility.The main body compartments that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurological disorders, such as brain damage, mental retardation, behavioral problems, nerve damage, and possibly Alzheimer's disease, Parkinsons disease, and schizophrenia. This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.

Papillary Meningioma Presenting as Rapidly Progressive Dementia and Parkinsonism

There are a variety of different causes of parkinsonism including PD, secondary parkinsonism, and the parkinsonism plus syndromes. Secondary parkinsonism is caused by structural, toxic, metabolic, or infectious mechanisms. Among structural causes, intracranial neoplasms are a rare cause of secondary parkinsonism. Moreover, there are almost never case reports with intracranial space-occupying lesions resulting in parkinsonism associated with rapid cognitive impairment. Therefore, we report herein a 37-year-old woman diagnosed with papillary meningioma who presented with parkinsonism associated with rapidly progressive cognitive impairment mimicking diffuse Lewy body disease.

Therapeutic effect of a natural squamosamide derivative FLZ on Parkinson's disease model mice induced by LPS plus MPTP / 药学学报

The aim of this study is to investigate the protective effect of N-[2-(4-hydroxyphenyl)ethyl]-2-(2, 5-dimethoxyphenyl)-3-(3-methoxy-4-hydroxyphenyl)acrylamide (FLZ), a novel synthetic squamosamide cyclic derivative, against Parkinson's disease (PD) model mice induced by the inflammatory bacterial endotoxin, lipopolysaccharides (LPS) and the neurotoxin 1-methy-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). C57/BL mice were ip injected LPS (5 mg x kg(-1)) once. One week following the LPS injection, mice received a subcutaneous injection of MPTP (25 mg x kg(-1)) once daily for 2 days. Eight weeks later, FLZ (25, 50 and 75 mg x kg(-1)) was orally administered to mice once daily for 60 days. The motor ability of the mice was evaluated by rod climbing test and footprint test. The dopamine (DA) levels in mouse striatum were determined by high performance liquid chromatography system. The tyrosine hydroxylase (TH)-positive cells were showed by immunohistochemical analysis. FLZ treatment significantly improved motor dysfunction of mice challenged by LPS plus MPTP. The increase of TH-positive cell numbers and elevation of DA levels may be contributed to the beneficial effects of FLZ on motor behavior. This study showed FLZ has significant therapeutic effect on LPS plus MPTP induced chronic PD model, which indicates its potential as a new candidate drug to treat PD.

Protection against neurotoxicity by an autophagic mechanism

The objective of the present study was to investigate the effects of 3-n-butylphthalide (NBP) on a 1-methyl-4-phenylpyridinium (MPP+)-induced cellular model of Parkinson’s disease (PD) and to illustrate the potential mechanism of autophagy in this process. For this purpose, rat PC12 pheochromocytoma cells were treated with MPP+ (1 mM) for 24 h following pretreatment with NBP (0.1 mM). Cell metabolic viability was determined by the MTT assay and cell ultrastructure was examined by transmission electron microscopy. The intracellular distribution and expression of α-synuclein and microtubule-associated protein light chain 3 (LC3) were detected by immunocytochemistry and Western blotting. Our results demonstrated that: 1) NBP prevented MPP+-induced cytotoxicity in PC12 cells by promoting metabolic viability. 2) NBP induced the accumulation of autophagosomes in MPP+-treated PC12 cells. 3) Further study of the molecular mechanism demonstrated that NBP enhanced the colocalization of α-synuclein and LC3 and up-regulated the protein level of LC3-II. These results demonstrate that NBP protects PC12 cells against MPP+-induced neurotoxicity by activating autophagy-mediated α-synuclein degradation, implying that it may be a potential effective therapeutic agent for the treatment of PD.

Astrocytoma in the Third Ventricle and Hypothalamus Presenting with Parkinsonism

Parkinsonism secondary to intracranial mass lesions usually results from compression or distortion of the basal ganglia. Secondary parkinsonism due to midbrain infiltration or compression is rare and generally associated with other neurologic signs caused by pyramidal tract and/or cranial nerve involvement. We report a case of 30-year-old woman in whom mild parkinsonism was the major clinical manifestation of an astrocytoma in the anterior third ventricle and hypothalamus. She underwent surgical resection, ventriculoperitoneal shunt and radiation therapy. All symptoms of parkinsonism were completely recovered 3 months after the treatment. Brain tumors can be manifested only by the symptoms of parkinsonism. This case emphasizes the significance of neuroimaging in the evaluation of parkinsonism.

Manganese and Parkinson's disease: a critical review and new findings / Manganês e doença de Parkinson: uma revisão crítica e novas descobertas

The goal of this review was to examine whether chronic Mn exposure produces dopamine neuron degeneration and PD or whether it has a distinct neuropathology and clinical presentation. I reviewed available clinical, neuroimaging, and neuropathological studies in humans and nonhuman primates exposed to Mn or other human conditions that result in elevated brain Mn concentrations. Human and nonhuman primate literature was examined to compare clinical, neuroimaging, and neuropathological changes associated with Mn-induced parkinsonism. Clinical, neuroimaging, and neuropathological evidence was used to examine whether Mn-induced parkinsonism involves degeneration of the nigrostriatal dopaminergic system as is the case in PD. The overwhelming evidence shows that Mn-induced parkinsonism does not involve degeneration of midbrain dopamine neurons and that l-dopa is not an effective therapy. New evidence is presented on a putative mechanism by which Mn may produce movement abnormalities. Confirmation of this hypothesis in humans is essential to make rational decisions about treatment, devise effective therapeutic strategies, and set regulatory guidelines.

O objetivo desta revisão foi examinar se a exposição crônica ao Mn produz degeneração do neurônio pela dopamina e DP ou se é apenas uma apresentação neuropatológica e clínica diferente. Foram revisados estudos clínicos, de neuroimagens e neuropatológicos disponíveis sobre humanos e primatas expostos ao Mn ou outras condições humanas que resultam em concentrações elevadas de Mn no cérebro. Foi examinada a literatura sobre humanos e primatas e comparadas as mudanças clínicas de neuroimagem e neuropatológicas associadas com o "parkinsonimo" induzido por Mn, envolvendo a degeneração do sistema dopaminérgico nigro-estriatal como no caso da DP. as evidências decisivas mostram que o "parkinsonismo" induzido pelo Mn não envolve a degeneração dos neurônios de dopamina do mesencéfalo e que o dopa-1 não é uma terapia eficaz. Novas evidências estão presentes em um mecanismo putativo pelo qual o Mn pode produzir anormalidades de movimento. A confirmação desta hipótese em humanos é essencial para tomar decisões adequadas sobre o tratamento, planejar estratégias terapêuticas eficazes e estabelecer guias regulatórios.

High-frequency electro-acupuncture stimulation modulates intracerebral γ-aminobutyric acid content in rat model of Parkinson's disease / 生理学报

The purpose of the present study is to observe the effect of electro-acupuncture (EA) stimulation on intracerebral neurotransmitters in a rat model of Parkinson's disease (PD), and explore the possible mechanism. We used 6-hydroxydopamine (6-OHDA) injection in medial forebrain bundle (MFB) in the right brain of Sprague Dawley (SD) rat to establish the parkinsonian rat model, and randomly divided the PD rats into model and 100 Hz EA stimulation groups (n =10 in each group). EA stimulation group received 4 courses of EA stimulation on Baihui (GV-20) and Dazhui (GV-14) acupuncture points. Moreover, ten rats were randomly selected as sham operation group, only receiving normal saline (NS) injection in MFB. Then apomorphine (APO)-induced rotational behavior in different groups was recorded, and the contents of γ-aminobutyric acid (GABA) in the brain were analyzed with high pressure/performance liquid chromatography-electrochemical detection (HPLC-ECD). The results showed that model group exhibited abnormal rotational behavior with APO treatment, suggesting the successful establishment of PD model. Compared with sham operation group, model group showed increased GABA contents in cortex and striatum, as well as decreased GABA content in ventral midbrain, on the lesioned side. EA stimulation could effectively ameliorate the abnormal rotational behavior of PD rat. Compared with the model group, EA stimulation decreased the ratio of GABA content on the lesioned side to that on unlesioned side in the cortex, while increased the ratios in the striatum and cerebellum. However, there was no difference of the ratio in the ventral midbrain among three groups. These results suggest high-frequency EA stimulation significantly improves the abnormal behavior of PD rats, which may exert through enhancing the inhibitory effect of cerebellum-basal ganglia-cortical loop on motor center.