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1.
Hum Mutat ; 41(4): 807-824, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31898848

RESUMO

Minisatellites, also called variable number of tandem repeats (VNTRs), are a class of repetitive elements that may affect gene expression at multiple levels and have been correlated to disease. Their identification and role as expression quantitative trait loci (eQTL) have been limited by their absence in comparative genomic hybridization and single nucleotide polymorphisms arrays. By taking advantage of cap analysis of gene expression (CAGE), we describe a new example of a minisatellite hosting a transcription start site (TSS) which expression is dependent on the repeat number. It is located in the third intron of the gene nitrogen permease regulator like protein 3 (NPRL3). NPRL3 is a component of the GAP activity toward rags 1 protein complex that inhibits mammalian target of rapamycin complex 1 (mTORC1) activity and it is found mutated in familial focal cortical dysplasia and familial focal epilepsy. CAGE tags represent an alternative TSS identifying TAGNPRL3 messenger RNAs (mRNAs). TAGNPRL3 is expressed in red blood cells both at mRNA and protein levels, it interacts with its protein partner NPRL2 and its overexpression inhibits cell proliferation. This study provides an example of a minisatellite that is both a TSS and an eQTL as well as identifies a new VNTR that may modify mTORC1 activity.


Assuntos
Proteínas Ativadoras de GTPase/metabolismo , Regulação da Expressão Gênica , Repetições Minissatélites , Sítio de Iniciação de Transcrição , Linhagem Celular , Proteínas Ativadoras de GTPase/genética , Genômica/métodos , Genótipo , Humanos , Íntrons , Família Multigênica , Polimorfismo Genético , Capuzes de RNA , Interferência de RNA , RNA Interferente Pequeno
2.
Sci Rep ; 9(1): 6151, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30992490

RESUMO

Early diagnosis of Parkinson's disease (PD) remains a challenge to date. New evidence highlights the potential clinical value of circulating trace amines (TAs) in early-stage PD and their involvement in disease progression. A new ultra performance chromatography mass spectrometry (UPLC-MS/MS) method was developed to quantify plasmatic TAs, and the catecholamines and indolamines pertaining to the same biochemical pathways. Three groups of subjects were recruited: 21 de novo, drug untreated, PD patients, 27 in treatment PD patients and 10 healthy subjects as controls. Multivariate and univariate data analyses were applied to reveal metabolic changes among the groups in attempt to discover new putative markers for early PD detection and disease progression. Different circulating levels of tyrosine (p = 0.002), tyramine (p < 0.001), synephrine (p = 0.015), norepinephrine (p = 0.012), metanephrine (p = 0.001), ß-phenylethylamine (p = 0.001) and serotonin (p = 0.006) were found among the three groups. While tyramine behaves as a putative biomarker for early-stage PD (AUC = 0.90) tyramine, norepinephrine, and tyrosine appear to act as biomarkers of disease progression (AUC > 0.75). The findings of this pilot cross-sectional study suggest that biochemical anomalies of the aminergic and indolic neurotransmitters occur in PD patients. Compounds within the TAs family may constitute putative markers for early stage detection and progression of PD.


Assuntos
Aminas Biogênicas/sangue , Doença de Parkinson/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Progressão da Doença , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Doença de Parkinson/diagnóstico , Serotonina/sangue , Sinefrina/sangue , Tiramina/sangue , Tirosina/sangue
3.
J Stroke Cerebrovasc Dis ; 25(9): 2196-202, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27425766

RESUMO

OBJECTIVE: Stroke is one of the leading causes of disability and death in the world. The endocannabinoid (eCB) system is upregulated in several neurological diseases including stroke. A previous animal study demonstrated an increased expression of the endocannabinoid receptor 1 (CB1R) in the penumbra area surrounding the ischemic core, suggesting a crucial role in inflammation/reperfusion after stroke. Regarding the localization of CB1/CB2 receptors, animal studies showed that cortical neurons, activated microglia, and astroglia are involved. Our aim was to evaluate the cerebral expression of CB1R in the ischemic brain areas of 9 patients who died due to acute cerebral infarction in the middle cerebral artery territory. METHODS: The cerebral autoptic tissue was collected within 48 hours since death. Ischemic and contralateral normal-appearing areas were identified. After tissue preprocessing, 4-µm-thick cerebral sections were incubated with the primary CB1R antibodies (Cayman Chemical Company, Ann Arbor, MI). Thereafter, all cerebral sections were hematoxylin treated. In each section, the total cell number and CB1R-positive cells were counted and the CB1R-positive cell count ratio was calculated. For statistical analysis, Student's t-test was used. RESULTS: In normal tissue, CB1R-positive neurons were the majority; a few non-neuronal cells expressed CB1R. In the ischemic areas, a few neurons were detectable. A significant increase in total CB1R staining was found in the ischemic regions compared to contralateral areas. CONCLUSIONS: We found an increase in CB1R expression in the ischemic region (neuronal and non-neuronal cell staining), suggesting the inflammatory reaction to the ischemic insult. Whether such response might mediate neuroprotective actions or excitotoxicity-related detrimental effects is still unclear.


Assuntos
Autopsia , Córtex Cerebral/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , Regulação para Cima/genética , Idoso , Idoso de 80 Anos ou mais , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Feminino , Humanos , Masculino , Mudanças Depois da Morte , Estudos Retrospectivos , Estatística como Assunto , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X
4.
BMC Genomics ; 16: 876, 2015 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-26510930

RESUMO

BACKGROUND: Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. METHODS: Changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls ("Discovery set") were analyzed by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. Data analysis was performed by applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays. Functional annotations were assigned using GO, DAVID, GSEA to unveil significant enriched biological processes in the differentially expressed genes. The expressions of selected genes were validated using RT-qPCR and samples from an independent cohort of 12 patients and controls ("Validation set"). RESULTS: Gene expression profiling of blood samples discriminates PD patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts as CBX5, TCF3, MAN1C1 and DOCK10 were validated by RT-qPCR. CONCLUSIONS: Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention.


Assuntos
Doença de Parkinson/genética , Transcriptoma/genética , Idoso , Homólogo 5 da Proteína Cromobox , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real
5.
Br J Psychiatry ; 206(2): 145-52, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25431431

RESUMO

BACKGROUND: Dementia with Lewy bodies (DLB) is underrecognised in clinical settings. AIMS: To investigate whether performing a (123)I-ioflupane injection ((123)I-FP-CIT also called DaTSCAN™) single photon emission computed tomography (SPECT) scan in patients with possible DLB would lead to a more certain diagnosis (probable DLB or non-DLB dementia). METHOD: We randomised 187 patients with possible DLB 2:1 to have a scan or not (control group). The outcome measure was a change in diagnosis to probable DLB or non-DLB. RESULTS: There were 56 controls and 114 scanned patients, of whom 43% had an abnormal scan. More patients in the imaging group had a change in diagnosis compared with controls at 8 and 24 weeks (61% (n = 70) v. 4% (n = 2) and 71% (n = 77) v. 16% (n = 9); both P<0.0001). Clinicians were more likely to change the diagnosis if the scan was abnormal (82%) than if it was normal (46%). CONCLUSIONS: Imaging significantly contributed to a more certain diagnosis, proving to be a useful adjunct in the work-up of patients with possible DLB.


Assuntos
Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Doença por Corpos de Lewy/diagnóstico por imagem , Nortropanos , Tomografia Computadorizada de Emissão de Fóton Único , Idoso , Encéfalo/metabolismo , Feminino , Humanos , Masculino , Valor Preditivo dos Testes
6.
J Neuroimaging ; 24(3): 273-7, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23279290

RESUMO

BACKGROUND: Recent studies suggest that alterations in the cerebrospinal venous system may play a role in multiple sclerosis (MS) and that chronic cerebrospinal venous insufficiency correlates with clinical features of MS patients. OBJECTIVES: To evaluate the vascularization of optic nerve (ONr) and measure ONe thickness by color Doppler ultrasonography in MS patients with and without previous optic neuritis (ONe). SUBJECTS AND METHODS: We assessed flow variables in the ophthalmic artery, central retinal artery, and central retinal vein and measured the diameter of ONe in 46 relapsing-remitting MS patients and 37 healthy controls (HC). Twenty-two MS patients had previous ONe and 24 MS patients had not. Patients with acute ONe were not included. We examined and compared 63 unaffected and 29 affected eyes of MS patients with 74 control eyes. RESULTS: Regarding flow variables, we did not find any significant difference between HC, MS affected, and unaffected eyes. Comparing ONr diameters, we found a progressive significant thinning of the ONr from HC to MS patients without and with past ONe. CONCLUSIONS: We found no significant alteration in the arterial-venous vascularization of both affected and unaffected ONr compared with HC. We demonstrated the possibility to detect ONr atrophy in MS patients.


Assuntos
Esclerose Múltipla/diagnóstico por imagem , Artéria Oftálmica/diagnóstico por imagem , Nervo Óptico/irrigação sanguínea , Nervo Óptico/diagnóstico por imagem , Neurite Óptica/diagnóstico por imagem , Artéria Retiniana/diagnóstico por imagem , Veia Retiniana/diagnóstico por imagem , Adulto , Feminino , Humanos , Masculino , Esclerose Múltipla/complicações , Neurite Óptica/etiologia , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Ultrassonografia
7.
Front Hum Neurosci ; 7: 803, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24324426

RESUMO

The premotor cortex is one of the fundamental structures composing the neural networks of the human brain. It is implicated in many behaviors and cognitive tasks, ranging from movement to attention and eye-related activity. Therefore, neural circuits that are related to premotor cortex have been studied to clarify their connectivity and/or role in different tasks. In the present work, we aimed to investigate the propagation of the neural activity evoked in the dorsal premotor cortex using transcranial magnetic stimulation/electroencephalography (TMS/EEG). Toward this end, interest was focused on the neural dynamics elicited in long-ranging temporal and spatial networks. Twelve healthy volunteers underwent a single-pulse TMS protocol in a resting condition with eyes closed, and the evoked activity, measured by EEG, was compared to a sham condition in a time window ranging from 45 ms to about 200 ms after TMS. Spatial and temporal investigations were carried out with sLORETA. TMS was found to induce propagation of neural activity mainly in the contralateral sensorimotor and frontal cortices, at about 130 ms after delivery of the stimulus. Different types of analyses showed propagated activity also in posterior, mainly visual, regions, in a time window between 70 and 130 ms. Finally, a likely "rebounding" activation of the sensorimotor and frontal regions, was observed in various time ranges. Taken together, the present findings further characterize the neural circuits that are driven by dorsal premotor cortex activation in healthy humans.

8.
Neuroepidemiology ; 41(1): 54-61, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23711404

RESUMO

BACKGROUND: We conducted a retrospective population-based study to estimate the incidence of amyotrophic lateral sclerosis (ALS) in Friuli Venezia Giulia, Italy, from 2001 to 2009. METHODS: Multiple sources were used for case ascertainment: Health databases, archives of the neurology departments and of the regional chapter of the Italian ALS Association. The diagnosis was validated through clinical documentation review. Crude and standardized incidence rates (IRs) per 100,000 person-years were calculated. RESULTS: We identified 262 incident ALS cases, 50.4% men, 4.2% familial. Half of the patients had spinal onset (56.8% in men) and 25.2% bulbar (29% in women). Bulbar onset had a similar frequency in women (31.7%) and men (31.5%) aged 67 or above at diagnosis. The crude IR was 2.72 (95% confidence interval, 95% CI, 2.39-3.05) and the male:female ratio 1.08. The IR peaked in the 65-74 age group, with a second increase in men 85 years and older. The IR standardized to the 2001 Italian population was 2.38 (95% CI 2.13-2.63) and to the 2000 European population 2.58 (95% CI 2.34-2.81). CONCLUSIONS: This retrospective study found IRs of ALS in the range of Italian and European prospective population-based registries, suggesting an almost complete case ascertainment.


Assuntos
Esclerose Lateral Amiotrófica/epidemiologia , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Sistema de Registros , Estudos Retrospectivos , Distribuição por Sexo
9.
Cortex ; 49(3): 781-92, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22225881

RESUMO

INTRODUCTION: Developmental stuttering (DS) is viewed as a motor speech-specific disorder, although several lines of research suggest that DS is a symptom of a broader motor disorder. We investigated corticospinal excitability in adult DS and normal speakers. METHODS: Transcranial magnetic stimulation (TMS) was administered over left/right hand representation of the motor cortex while recording motor evoked potentials (MEPs) from the contralateral first dorsal interosseous (FDI) muscle. Resting, active motor thresholds, silent period threshold and duration were measured. A stimulus-response curve at resting was also obtained to evaluate MEP amplitudes. RESULTS: Lower corticospinal responses in the left hemisphere of DS were found, as indicated by a reduction of peak-to-peak MEP amplitudes compared to normal speakers. CONCLUSIONS: This provides further evidence that DS may be a general motor deficit that also involves motor non-speech-related structures. Moreover, our results confirm that DS may be related to left hemisphere hypoactivation and/or lower left hemisphere dominance. The present data and protocol may be useful for diagnosis of subtypes of DS that may benefit from pharmacological treatment by targeting the general level of cortical excitability.


Assuntos
Potencial Evocado Motor/fisiologia , Lateralidade Funcional/fisiologia , Córtex Motor/fisiopatologia , Tratos Piramidais/fisiopatologia , Gagueira/fisiopatologia , Adulto , Estimulação Elétrica , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiologia , Estimulação Magnética Transcraniana
11.
Front Neuroeng ; 5: 18, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22891059

RESUMO

To better define the neural networks related to preparation of reaching, we applied transcranial magnetic stimulation (TMS) to the lateral parietal and frontal cortex. TMS did not evoke effects closely related to preparation of reaching, suggesting that neural networks already identified by our group are not larger than previously thought. We also replicated previous TMS/EEG data by applying TMS to the parietal cortex: new analyses were performed to better support reliability of already reported findings (Zanon et al., 2010; Brain Topography 22, 307-317). We showed the existence of neural circuits ranging from posterior to frontal regions of the brain after the stimulation of parietal cortex, supporting the idea of strong connections among these areas and suggesting their possible temporal dynamic. Connection with ventral stream was confirmed. The present work helps to define those areas which are involved in preparation of natural reaching in humans. They correspond to parieto-occipital, parietal and premotor medial regions of the left hemisphere, i.e., the contralateral one with respect to the moving hand, as suggested by previous studies. Behavioral data support the existence of a discrete stream involved in reaching. Besides the serial flow of activation from posterior to anterior direction, a parallel elaboration of information among parietal and premotor areas seems also to exist. Present cortico-cortical interactions (TMS/EEG experiment) show propagation of activity to frontal, temporal, parietal and more posterior regions, exhibiting distributed communication among various areas in the brain. The neural system highlighted by TMS/EEG experiments is wider with respect to the one disclosed by the TMS behavioral approach. Further studies are needed to unravel this paucity of overlap. Moreover, the understanding of these mechanisms is crucial for the comprehension of response inhibition and changes in prepared actions, which are common behaviors in everyday life.

12.
J Neurol Sci ; 320(1-2): 161-5, 2012 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-22836016

RESUMO

In multiple sclerosis (MS), brain-derived neurotrophic factor (BDNF) provides neuroprotection, but can also promote disease through the maintenance of autoreactive T cells. One aspect that has not been explored yet in MS is related to the opposite functions of BDNF protein isoforms consisting of the pro-BDNF precursor, which has pro-apoptotic effects, and two proteolytic isoforms, the mature BDNF with pro-survival effects and truncated BDNF, with unknown functions. Using ELISA and semi-quantitative Western-blot we determined the relative serum levels of BDNF isoforms in 20 relapsing-remitting MS patients without any disease modifying therapy and 20 age and gender-matched healthy controls and searched for clinical correlates. Total serum BDNF was lower in MS than in HC. We demonstrate that the capture and detection antibodies of the ELISA kit from Promega are able to recognize all three isoforms but with different efficiency. Using Western-blot analysis, we show that the percentage of serum mature BDNF and pro-BDNF with respect to total serum BDNF was significantly decreased, while truncated BDNF was increased. No correlation between BDNF isoform percentage and clinical or demographic features was found. Serum Fas (sFas) was increased. These results support and expand the current hypothesis on the role of BDNF in multiple sclerosis, in that low pro-BDNF and high sFas might result in a failure to limit autoreactive T cells by apoptotic deletion and decreased mature BDNF may not provide enough neuroprotection, while truncated BDNF percent increase could be a compensatory mechanism. Hence, future studies on MS should take into account BDNF proteolytic processing.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Esclerose Múltipla Recidivante-Remitente/metabolismo , Esclerose Múltipla/metabolismo , Isoformas de Proteínas/metabolismo , Receptor fas/metabolismo , Adulto , Fator Neurotrófico Derivado do Encéfalo/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/sangue , Esclerose Múltipla Recidivante-Remitente/sangue , Isoformas de Proteínas/sangue , Precursores de Proteínas/sangue , Precursores de Proteínas/metabolismo , Receptor fas/sangue
13.
Artigo em Inglês | MEDLINE | ID: mdl-22291623

RESUMO

Stereotactic technique and the introduction of deep brain stimulation (DBS) can be considered two milestones in the field of surgical neuromodulation. At present the role of DBS in the treatment of clinically and epidemiologically relevant movement disorders is widely accepted and DBS procedures are performed in many clinical centers worldwide. Here we review the current state of the art of DBS treatment for the most common movement disorders: Parkinson's disease, essential tremor, and dystonia. In this review, we give a brief description of the candidate patient selection criteria, the different anatomical targets for each of these condition, and the expected outcomes as well as possible side effects.

14.
Rehabil Res Pract ; 2011: 670537, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22110978

RESUMO

The objective of the study was to treat fatigue in patients with multiple sclerosis (MS) by a neurocognitive rehabilitation program aimed at improving motor planning by using motor imagery (MI). Twenty patients with clinically definite MS complaining of fatigue were treated for five weeks with exercises of neurocognitive rehabilitation twice a week. Patients were evaluated by Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), MSQoL54, Expanded Disability Status Scale (EDSS), and MS Functional Composite (MSFC). After treatment, a decrease in fatigue was detected with both FSS (P = 0.0001) and MFIS (P = 0.0001). MSFC (P = 0.035) and MSQoL54 (P = 0.002) scores improved compared to baseline. At six-month followup, the improvement was confirmed for fatigue (FSS, P = 0.0001; MFIS P = 0.01) and for the physical subscale of MSQoL54 (P = 0.049). No differences in disability scales were found. These results show that neurocognitive rehabilitation, based on MI, could be a strategy to treat fatigue in MS patients.

17.
Lipids Health Dis ; 9: 47, 2010 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-20470384

RESUMO

BACKGROUND: Endocannabinoids (eCBs) are ubiquitous lipid mediators that act on specific (CB1, CB2) and non-specific (TRPV1, PPAR) receptors. Despite many experimental animal studies proved eCB involvement in the pathogenesis of stroke, such evidence is still lacking in human patients. Our aim was to determine eCB peripheral levels in acute stroke patients and evaluate their relationship with clinical disability and stroke volume. METHODS: A cohort of ten patients with a first acute (within six hours since symptoms onset) ischemic stroke and a group of eight age- and sex-matched normal subjects were included. Groups were also matched for metabolic profile. All subjects underwent a blood sample collection for anandamide (AEA), 2-arachidonoylglycerol (2-AG) and palmitoylethanolamide (PEA) measurement; blood sampling was repeated in patients on admission (T0), at 6 (T1) and 18 hours (T2) thereafter. Patients neurological impairment was assessed using NIHSS and Fugl-Meyer Scale arm subitem (FMSa); stroke volume was determined on 48 h follow-up brain CT scans. Blood samples were analyzed by liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry. RESULTS: 1)T0 AEA levels were significantly higher in stroke patients compared to controls. 2)A significant inverse correlation between T0 AEA levels and FMSa score was found. Moreover a positive correlation between T0 AEA levels and stroke volume were found in stroke patients. T0 PEA levels in stroke patients were not significantly different from the control group, but showed a significant correlation with the NIHSS scores. T0 2-AG levels were lower in stroke patients compared to controls, but such difference did not reach the significance threshold. CONCLUSIONS: This is the first demonstration of elevated peripheral AEA levels in acute stroke patients. In agreement with previous murine studies, we found a significant relationship between AEA or PEA levels and neurological involvement, such that the greater the neurological impairment, the higher were these levels.


Assuntos
Ácidos Araquidônicos/sangue , Ácidos Palmíticos/sangue , Alcamidas Poli-Insaturadas/sangue , Acidente Vascular Cerebral/etiologia , Idoso , Idoso de 80 Anos ou mais , Amidas , Moduladores de Receptores de Canabinoides/sangue , Cromatografia Líquida , Endocanabinoides , Etanolaminas , Glicerídeos/sangue , Humanos , Masculino , Espectrometria de Massas , Metabolômica , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/diagnóstico
18.
Neurosci Lett ; 469(3): 348-51, 2010 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-20026245

RESUMO

Recent evidence suggests that trace amines such as tyramine and octopamine, alternative products of tyrosine metabolism (an aminoacid parent of dopamine and noradrenaline), play a role in the homeostasis of the extrapyramidal system. However, the relevance of these trace amines in the pathogenesis of Parkinson's disease is still largely unknown. Here, we assessed the plasma levels of octopamine and noradrenaline in three sub-groups of PD patients, namely de novo, non-fluctuating and fluctuating patients, versus age-matched control subjects. We show that octopamine is detectable in plasma of all subjects, the mean levels of which are significantly lower in PD patients, including de novo patients, when compared to controls (p<0.001). Unlike this, no changes in plasmatic noradrenaline levels were found in the de novo patients, but only in plasma of fluctuating and non-fluctuating PD patients. These findings raise the possibility that Parkinson's disease is firstly characterized by abnormalities of tyrosine decarboxylase, rather than tyrosine hydroxylase, enzyme activity. Given the role of this enzyme in the production of trace amines, circulating octopamine levels may hold promise as a biomarker of early Parkinson's disease.


Assuntos
Norepinefrina/sangue , Octopamina/sangue , Doença de Parkinson/sangue , Idoso , Aminas/metabolismo , Biomarcadores/sangue , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/metabolismo , Octopamina/metabolismo , Doença de Parkinson/metabolismo , Fatores de Tempo
19.
Brain Topogr ; 22(4): 307-17, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19499197

RESUMO

Parietal cortex subserves various cognitive tasks, ranging from attention to visuo-motor skills. It is part of a parieto-frontal network involved in attention, and part of the visual dorsal stream, opposed to the visual ventral stream, although increasing evidence suggests interchange of information between them. In this study, co-registration of Transcranial Magnetic Stimulation (TMS) and Electroencephalographic activity (EEG) has been used to investigate the spreading of cortical connections from the parietal cortex in healthy volunteers. TMS on the left parietal cortex activated a network of prefrontal regions in the contra-lateral hemisphere in a time range of 102-167 ms after the stimulus. Moreover, activation in the ipsi-lateral middle temporal and fusiform gyri was observed at 171-177 ms after delivery of TMS. Findings suggest the existence of late driven connections between parietal and prefrontal regions that could partially represent the neural pathway related to attention, even if, in this experiment, no attentional processing was requested. Late connections between dorsal and ventral streams were also evident, confirming previous evidence about interchange of information between them. Conclusively, the present investigation confirms that a great amount of information spreads from parietal cortex to different regions in the brain, supporting the idea that connections are more complex and articulated than those proposed. Present findings also suggest that the simultaneous recording of EEG during the application of TMS is a promising tool for the study of connections in the brain.


Assuntos
Encéfalo/fisiologia , Vias Visuais/fisiologia , Adulto , Mapeamento Encefálico/métodos , Eletroencefalografia/métodos , Potenciais Evocados , Feminino , Humanos , Masculino , Processamento de Sinais Assistido por Computador , Fatores de Tempo , Estimulação Magnética Transcraniana/métodos , Adulto Jovem
20.
Behav Brain Res ; 201(1): 112-9, 2009 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-19428624

RESUMO

A large amount of evidence supports a role for the parietal and frontal cortex in the planning of reaching movements. Nevertheless, neither the timing of involvement of these areas nor if and how their activity can be influenced by external stimuli has been clarified. The parieto-occipital cortex has been investigated by applying transcranial magnetic stimulation (TMS) at 25% (Time 1), 50% (Time 2) and 75% (Time 3) of the reaction time from a go signal to hand movement. No local effect was found with Time 1, since pulses were administered before subjects opened their eyes. Reduction of reaction time was observed at Time 2 when stimuli were applied over the anterior occipital lobe, parieto-occipital cortex and posterior parietal cortex. The effect on the posterior parietal cortex reverted when Time 3 was used. The present data confirm the existence, in humans, of a dorso-medial set of areas involved in on-line planning of reaching movements. Moreover, they provide novel evidence on the time course of this involvement. Finally, present data show that it is possible to interact with the flow of activity along this stream by appropriately delivering TMS pulses.


Assuntos
Braço , Cognição/fisiologia , Lobo Occipital/fisiologia , Lobo Parietal/fisiologia , Desempenho Psicomotor/fisiologia , Adulto , Análise de Variância , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tempo de Reação , Estimulação Magnética Transcraniana , Adulto Jovem
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