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1.
Life Sci ; 240: 117091, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31760102

RESUMO

Mounting evidences indicated that elevated iron levels in the substantia nigra (SN) have been concerned as the underlying mechanisms of neurodegenerative diseases, including Parkinson's disease (PD). The present study used the 1-Methyl-4-phenyl-1, 2, 3, 6 -tetrahydropyridine (MPTP)-treated cynomolgus monkeys for PD to evaluate the usability of SWI for assessing iron deposition in the cerebral nuclei of PD. The results showed that susceptibility-weighted imaging (SWI) phase values of the ipsilateral (MPTP-lesion side) SN of MPTP-treated monkeys were lower than those in the contralateral SN of MPTP-treated monkeys and the same side of Control monkeys, suggesting that iron deposition were elevated in the affected side SN of MPTP-treated monkeys. Whereas MPTP has not effects on the SWI phase values in other detected brain regions of monkeys, including red nucleus (RN), putamen (PUT) and caudate nucleus (CA). Furthermore, ICP-MS results showed that MPTP increased the iron levels in MPTP injection side, but no in the ipsilateral striatum. Additionally, MPTP treatment did not affect the calcium and manganese levels in the detected brain regions of monkeys. However, Pearson correlation analysis results indicated that there were not relationship between SWI phase values in MPTP-lesion side of SN with the behavioral score, tyrosine hydroxylase (TH)-positive cells number and iron levels in the MPTP-lesion side of midbrain. Taken together, the results confirm the involvement of SN iron accumulations in the MPTP-treated monkey models for PD, and indirectly verify the usability of SWI for the measurement of iron deposition in the cerebral nuclei of PD.


Assuntos
Ferro/metabolismo , Intoxicação por MPTP/metabolismo , Transtornos Parkinsonianos/metabolismo , Animais , Comportamento Animal , Encéfalo/diagnóstico por imagem , Cálcio/metabolismo , Intoxicação por MPTP/diagnóstico por imagem , Macaca fascicularis , Imagem por Ressonância Magnética , Masculino , Manganês/metabolismo , Espectrometria de Massas , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/diagnóstico por imagem , Substância Negra/metabolismo , Substância Negra/patologia , Tirosina 3-Mono-Oxigenase/metabolismo
2.
Curr Med Sci ; 39(5): 831-835, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31612404

RESUMO

Recent researches have found that 7 Tesla SWI can detect the alteration of substantia nigra hyperintensity in Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). The aim of this study was to investigate whether 3 Tesla SWI (3T SWI) can visualize anatomical alterations occurring in a hyperintense structure of the substantia nigra in PD and vascular parkinsonism (VP), and whether the evaluation of abnormal signal can be used as a factor in the differential diagnosis of PD and VP. Using 3 Tesla MRI, we evaluated 38 healthy subjects, 33 patients with PD and 34 patients with VP. Two blinded readers independently assessed the images. We found that the dorsolateral nigral hyperintensity was absent in 31 of 33 patients with PD and 15 of 34 patients with VP. The dorsolateral nigral hyperintensity was present in 19 of 34 patients with VP and 35 of 38 healthy controls. Group comparisons of absence of dorsolateral nigral hyperintensity revealed significant differences between the patients with PD and those with VP (P<0.001). The sensitivity of SWI for PD was 93.9% and the specificity was 92.1%. Visual assessment of dorsolateral nigral hyperintensity on high-field SWI scans may serve as a new simple diagnostic imaging marker for PD. And our study results indicate that 3T SWI can be used as a tool to identify PD and VP.


Assuntos
Demência por Múltiplos Infartos/diagnóstico por imagem , Imagem por Ressonância Magnética/estatística & dados numéricos , Doença de Parkinson/diagnóstico por imagem , Substância Negra/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Estudos de Casos e Controles , Demência por Múltiplos Infartos/patologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/patologia , Sensibilidade e Especificidade , Substância Negra/irrigação sanguínea , Substância Negra/patologia
3.
Folia Neuropathol ; 57(3): 258-266, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588712

RESUMO

The peripheral inflammatory stimulus could induce cell damage in peripheral organs and activate microglial cells in the brain. One such stimulus was given to adult male Wistar rats by injecting different concentrations of lipopolysaccharide (LPS; 50, 300, 500 g/kg and 5 mg/kg i.p.). To verify the systemic effect of the LPS administration, the serum content of C-reactive protein (CRP), the variation of body weight and cellular changes in the spleen, liver and kidney were determined. Motor impairment was evaluated by rotarod and open field tests. Microglia activation and dopaminergic degeneration was confirmed by immunolabelling for CD11b/c (microglia) and tyrosine hydroxylase (TH), respectively. The cell counting was performed in substantia nigra pars compacta (SNpc), microglial activation was explored in SNpc, substantia nigra pars reticulata (SNpr), substantia nigra pars compacta dorsal (SNcd) and the ventral tegmental area (VTA). For the statistical analysis, one-way ANOVA followed by Tukey post hoc test (p ≤ 0.05) was used. On day 7 post intraperitoneal administration of LPS, cellular atrophy was detected in the liver, kidney and spleen at 5 mg/kg, without significant changes in CRP levels. Body weight loss and motor impairment was present only on day 1 post LPS administration. The dosage of 500 g/kg and 5 mg/kg of LPS caused the loss of dopaminergic neurons (40%) in SNpc and microglia migration in a dose-dependent manner in SNcd, SNpc and SNpr. LPS-induced endotoxemia favours damage to the peripheral organs and microglial migration in a dose-dependent manner in rat substantia nigra.


Assuntos
Endotoxemia/patologia , Lipopolissacarídeos/toxicidade , Microglia/patologia , Substância Negra/patologia , Animais , Movimento Celular , Neurônios Dopaminérgicos/patologia , Endotoxemia/induzido quimicamente , Masculino , Ratos , Ratos Wistar
4.
Sheng Li Xue Bao ; 71(5): 732-740, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31646327

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disease, characterized by loss of dopaminergic (DA) neurons in the dense part of the substantia nigra (SNpc). Postmortem analysis of PD patients and experimental animal studies found that microglial cell activation and increased levels of pro-inflammatory factors were common features of PD brain tissue. At the same time, the invasion and accumulation of peripheric immune cells were detected in the brain of PD patients. In this paper, peripheral inflammation across the blood-brain barrier (BBB), the misfolded α-synuclein (α-syn)-induced microglial cell activation and intracerebral inflammation in PD are summarized, providing potential therapeutic measures for delaying the onset of PD.


Assuntos
Inflamação/patologia , Doença de Parkinson/patologia , Substância Negra/patologia , Animais , Barreira Hematoencefálica , Neurônios Dopaminérgicos/patologia , Humanos , Microglia , alfa-Sinucleína
5.
C R Biol ; 342(5-6): 192-198, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474522

RESUMO

Exposure to lead is a threat factor for neurodegenerative disorders progress as it could trigger dopaminergic deficiency. We aimed herein to assess the effect of acute lead exposure (25mg/kg B.W i.p.) during three continuous days on the dopaminergic and noradrenergic systems together with locomotor performance in Meriones shawi (M. shawi), then the neuroprotective potential of curcumin-III (30mg/kg B.W) by oral gavage. Pb-exposed M. shawi exhibited increased tyrosine hydroxylase (TH) immunoreactivity in substantia nigra compacta (SNc), ventral tegmental area (VTA), locus coeruleus (LC), and dorsal striatum (DS), unlike the controls. This was correlated with decreased locomotor performance. A noticeable protective effect by co-treatment with curcumin-III was observed; in consequence, TH-immunoreactivity and locomotor disturbance were restored in Pb-treated Meriones. Our data results proved, on the one hand, an evident neurotoxic effect of acute Pb exposure and, on the other hand, a potent therapeutic effect of curcumin-III. Thereby, this compound may be recommended as a neuroprotective molecule for neurodegenerative disorders involving catecholaminergic impairment initiated by metallic elements.


Assuntos
Corpo Estriado/patologia , Curcumina/análogos & derivados , Neurônios Dopaminérgicos/efeitos dos fármacos , Intoxicação do Sistema Nervoso por Chumbo/tratamento farmacológico , Intoxicação do Sistema Nervoso por Chumbo/patologia , Fármacos Neuroprotetores/uso terapêutico , Sistema Nervoso Parassimpático/patologia , Substância Negra/patologia , Administração Oral , Animais , Curcumina/uso terapêutico , Gerbillinae , Locus Cerúleo/patologia , Masculino , Transtornos dos Movimentos/psicologia , Área Tegmentar Ventral/patologia
6.
Adv Exp Med Biol ; 1173: 45-66, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456205

RESUMO

The key molecular events that provoke Parkinson's disease (PD) are not fully understood. Iron deposit was found in the substantia nigra pars compacta (SNpc) of PD patients and animal models, where dopaminergic neurons degeneration occurred selectively. The mechanisms involved in disturbed iron metabolism remain unknown, however, considerable evidence indicates that iron transporters dysregulation, activation of L-type voltage-gated calcium channel (LTCC) and ATP-sensitive potassium (KATP) channels, as well as N-methyl-D-aspartate (NMDA) receptors (NMDARs) contribute to this process. There is emerging evidence on the structural links and functional modulations between iron and α-synuclein, and the key player in PD which aggregates in Lewy bodies. Iron is believed to modulate α-synuclein synthesis, post-translational modification, and aggregation. Furthermore, glia, especially activated astroglia and microglia, are involved in iron deposit in PD. Glial contributions were largely dependent on the factors they released, e.g., neurotrophic factors, pro-inflammatory factors, lactoferrin, and those undetermined. Therefore, iron chelation using iron chelators, the extracts from many natural foods with iron chelating properties, may be an effective therapy for prevention and treatment of the disease.


Assuntos
Ferro/metabolismo , Doença de Parkinson/fisiopatologia , alfa-Sinucleína/metabolismo , Animais , Canais de Cálcio Tipo L , Neurônios Dopaminérgicos/patologia , Humanos , Canais KATP , Receptores de N-Metil-D-Aspartato , Substância Negra/patologia
7.
Brain Nerve ; 71(8): 875-883, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31346144

RESUMO

Parkinson's disease (PD), a common neurodegenerative disorder, is characterized by selective degeneration of dopaminergic neurons in the substantia nigra. There is no effective treatment to delay or halt the progression of PD. The establishment of disease models, based on human biology, is therefore important for developing effective disease-modifying therapies. The recent progress of human induced pluripotent stem cell-associated technologies provides an opportunity to understand disease etiology, discover new drugs, and develop novel therapeutic interventions.


Assuntos
Células-Tronco Pluripotentes Induzidas , Doença de Parkinson/patologia , Neurônios Dopaminérgicos/patologia , Humanos , Modelos Biológicos , Substância Negra/patologia
8.
Molecules ; 24(15)2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31349553

RESUMO

In a recent study, we described the neuroprotective properties of VCE-003.2-an aminoquinone derivative of the non-psychotropic phytocannabinoid cannabigerol (CBG)-administered intraperitoneally (i.p.) in an inflammatory model of Parkinson's disease (PD). We also demonstrated that these properties derive from its activity on the peroxisome proliferator-activated receptor-γ, in particular at a regulatory site within this receptor type. In the present study, we wanted to further confirm this neuroprotective potential using an oral lipid formulation of VCE-003.2, developed to facilitate the clinical development of this phytocannabinoid derivative. To this end, we evaluated VCE-003.2, administered orally at two doses (10 and 20 mg/kg), to mice subjected to unilateral intrastriatal injections of lipopolysaccharide (LPS), a classic model of inflammation-driven neuronal deterioration that recapitulates characteristics of PD. The administration of VCE-003.2 to these mice showed, as expected, poor activity in the different motor tests (rotarod, computer-aided actimeter) used in experimental parkinsonism, in general due to the lack of evident changes in these behaviors by LPS lesion. However, VCE-003.2, at 20 mg/kg, was highly active in improving the changes detected in LPS-lesioned mice in the cylinder rearing test. In addition, the histopathological analysis of the basal ganglia revealed a trend towards recovery at 20 mg/kg VCE-003.2 in the loss of tyrosine hydroxylase-containing nigrostriatal neurons, as well as a complete reduction in the elevated LAMP-1 immunolabeling (reflecting autophagy impairment) caused by LPS lesion. These effects were not seen at 10 mg/kg. This was associated with a partial reduction in the intense glial reactivity provoked by LPS in the substantia nigra, in particular the astroglial reactivity labeled with glial fibrillary acidic protein. The analysis using qPCR in the striatum of proinflammatory mediators, such as tumor necrosis factor-α, interleukin-1ß, inducible nitric oxide synthase, and cyclooxygenase-2, showed that the marked elevations provoked by the LPS lesion tended to be, in general, attenuated by VCE-003.2 treatment, with the greatest effects normally found with the highest dose of 20 mg/kg. In summary, our data confirm the neuroprotective potential of an oral formulation of VCE-003.2 against neuronal injury in an in vivo model of PD based on neuroinflammation, and this study opens the possibility to further the development of oral VCE-003.2 in the clinic.


Assuntos
Canabinoides/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , PPAR gama/agonistas , Quinonas/farmacologia , Administração Oral , Animais , Biomarcadores , Canabinoides/administração & dosagem , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Imuno-Histoquímica , Mediadores da Inflamação , Camundongos , Neurônios/patologia , Fármacos Neuroprotetores/administração & dosagem , Transtornos Parkinsonianos , Quinonas/administração & dosagem , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Substância Negra/patologia
9.
PLoS One ; 14(5): e0217922, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31150514

RESUMO

To meet the need for Parkinson's disease biomarkers and evidence for amount and distribution of pathological changes, MRI diffusion tensor imaging (DTI) has been explored in a number of previous studies. However, conflicting results warrant further investigations. As tissue microstructure, particularly of the grey matter, is heterogeneous, a more precise diffusion model may benefit tissue characterization. The purpose of this study was to analyze the diffusion-based imaging technique restriction spectrum imaging (RSI) and DTI, and their ability to detect microstructural changes within brain regions associated with motor function in Parkinson's disease. Diffusion weighted (DW) MR images of a total of 100 individuals, (46 Parkinson's disease patients and 54 healthy controls) were collected using b-values of 0-4000s/mm2. Output diffusion-based maps were estimated based on the RSI-model combining the full set of DW-images (Cellular Index (CI), Neurite Density (ND)) and DTI-model combining b = 0 and b = 1000 s/mm2 (fractional anisotropy (FA), Axial-, Mean- and Radial diffusivity (AD, MD, RD)). All parametric maps were analyzed in a voxel-wise group analysis, with focus on typical brain regions associated with Parkinson's disease pathology. CI, ND and DTI diffusivity metrics (AD, MD, RD) demonstrated the ability to differentiate between groups, with strongest performance within the thalamus, prone to pathology in Parkinson's disease. Our results indicate that RSI may improve the predictive power of diffusion-based MRI, and provide additional information when combined with the standard diffusivity measurements. In the absence of major atrophy, diffusion techniques may reveal microstructural pathology. Our results suggest that protocols for MRI diffusion imaging may be adapted to more sensitive detection of pathology at different sites of the central nervous system.


Assuntos
Diagnóstico por Imagem , Imagem de Tensor de Difusão , Degeneração Neural/diagnóstico , Doença de Parkinson/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/patologia , Imagem de Difusão por Ressonância Magnética , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Degeneração Neural/diagnóstico por imagem , Degeneração Neural/patologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Substância Negra/diagnóstico por imagem , Substância Negra/patologia , Tálamo/diagnóstico por imagem , Tálamo/patologia
10.
Cells ; 8(6)2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-31208049

RESUMO

Parkinson's disease is associated with an increased risk of melanoma (and vice versa). Several hypotheses underline this link, such as pathways affecting both melanin and neuromelanin. For the first time, the fluorescence of melanin and neuromelanin is selectively accessible using a new method of nonlinear spectroscopy, based on a stepwise two-photon excitation. Cutaneous pigmentation and postmortem neuromelanin of Parkinson patients were characterized by fluorescence spectra and compared with controls. Spectral differences could not be documented, implying that there is neither a Parkinson fingerprint in cutaneous melanin spectra nor a melanin-associated fingerprint indicating an increased melanoma risk. Our measurements suggest that Parkinson's disease occurs without a configuration change of neuromelanin. However, Parkinson patients displayed the same dermatofluorescence spectroscopic fingerprint of a local malignant transformation as controls. This is the first comparative retrospective fluorescence analysis of cutaneous melanin and postmortem neuromelanin based on nonlinear spectroscopy in patients with Parkinson's disease and controls, and this method is a very suitable diagnostic tool for melanoma screening and early detection in Parkinson patients. Our results suggest a non-pigmentary pathway as the main link between Parkinson's disease and melanoma, and they do not rule out the melanocortin-1-receptor gene as an additional bridge between both diseases.


Assuntos
Melaninas/metabolismo , Melanoma/patologia , Doença de Parkinson/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Encéfalo/patologia , Estudos de Casos e Controles , Feminino , Fluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Mudanças Depois da Morte , Fatores de Risco , Pele/patologia , Pigmentação da Pele , Substância Negra/patologia
11.
Mol Biol Rep ; 46(4): 4293-4302, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31123907

RESUMO

This study aimed to investigate the therapeutic effects of intranasal administration of human endometrium-derived stem cells (HEDSCs) in the mouse model of Parkinson's disease (PD). Thirty days after intrastriatal injection of 6-OHDA, HEDSCs were administrated intranasally in three doses (104, 5 × 104 and 105 cells µl-1). During 120 days after stem cell administration, behavioral tests were examined. Then the mice were sacrificed and the fresh section of the substantia nigra pars compacta (SNpc) was used for detection of HEDSCs-GFP labeled by fluorescence microscopy method. In addition, immunohistochemistry was used to assay GFP, human neural Nestin, and tyrosine hydroxylase (TH) markers in the fixed brain tissue at the SNpc. Our data revealed that behavioral parameters were significantly improved after cell therapy. Fluorescence microscopy assay in fresh tissue and GFP analysis in fixed tissue were showed that the HEDSCs-GFP labeled migrated to SNpc. The data from immunohistochemistry revealed that the Nestin as a differential neuronal biomarker was expressed in SNpc. Also, TH as a dopaminergic neuron marker significantly increased after HEDSCs therapy in an optimized dose 5 × 104 cells µl-1. Our results suggest that intranasal administration of HEDSCs improve the PD symptoms in the mouse model of PD dose-dependent manner as a noninvasive method.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Doença de Parkinson/terapia , Administração Intranasal/métodos , Animais , Modelos Animais de Doenças , Neurônios Dopaminérgicos , Endométrio/metabolismo , Feminino , Humanos , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Nestina/análise , Substância Negra/patologia , Tirosina 3-Mono-Oxigenase/análise
12.
Mol Med Rep ; 19(6): 4989-4997, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31059019

RESUMO

The pathological process of Parkinson's disease (PD) is closely associated with the death of nigral neurons, for which an effective treatment has yet to be found. Lithium, one of the most widely certified anticonvulsant and mood­stabilizing agents, exhibits evident neuroprotective effects in the treatment of epilepsy and bipolar disorder. In the present study, the neuroprotective mechanisms by which lithium acts on a chronic 1­methyl­4­phenyl­1,2,3,6­tetrahydropyridine (MPTP) mouse model of PD were investigated by employing animal behavioral tests, immunohistochemistry, RT­PCR, and western blotting. The results revealed that, in open field tests, lithium treatment counteracted the reduction in movement distance as well as activity time induced by MPTP administration. The compound could also prolong the drop time of MPTP­treated mice in rotarod tests. Moreover, lithium treatment corrected the loss of nigral neurons, the increase of α­synuclein (SNCA) in substantia nigra as well as in the striatum of MPTP­treated mice, and decreased the methylation of SNCA intron 1 in DNA from the same regions. Furthermore, marked changes were observed in the expression of miRNAs including miR­148a, a potential inhibitor of DNMT1, in the MPTP­treated mice. These results suggested that the early application of lithium was important for alleviating the behavioral deficits experienced in the PD model, and that the neuroprotective action of lithium was achieved through a lithium­triggered miRNA regulation mechanism. Essentially, our findings indicated that lithium may be beneficial in the prevention and treatment of PD through the regulation of α­synuclein methylation.


Assuntos
Lítio/uso terapêutico , Intoxicação por MPTP/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , alfa-Sinucleína/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Modelos Animais de Doenças , Íntrons , Lítio/farmacologia , Intoxicação por MPTP/patologia , Masculino , Metilação/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Fármacos Neuroprotetores/farmacologia , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Substância Negra/patologia , alfa-Sinucleína/genética
13.
J Headache Pain ; 20(1): 53, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092190

RESUMO

BACKGROUND: Brainstem raphe (BR) hypoechogenicity in transcranial sonography (TCS) has been depicted in patients with major depression (MD) and in depressed patients with different neurodegenerative diseases. But, up to date, the association of BR alterations in TCS with depression in migraineurs has never been reported. This study was to investigate the possible role of BR examination via TCS in migraineurs with depression. METHODS: Forty two migraine without aura (MwoA) patients and 40 healthy controls were recruited. Echogenicity of lentiform nuclei (LN), caudate nuclei (CN), substantia nigra (SN) and brainstem raphe (BR) and width of the frontal horns of the lateral ventricles and the third ventricle were assessed with TCS. The diagnosis of depression was based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders IV (DSM -IV), and the severity of depression was measured by Hamilton Rating Scale for Depression (HAM-D) and Hospital Anxiety and Depression Scale depression subscale (HADS-D). RESULTS: There were no significant differences between migraineurs and controls in the width of frontal horn of the lateral ventricle (p = 0.955), width of third ventricle (p = 0.129) as well as in the echogenicity of SN (p = 0.942), CN (p = 0.053), LN (p = 0.052) and BR (p = 0.677). Here, it seems that more migraineurs were detected with increased echogenecity of CN and LN compared with controls (33.3% versus 15.0% for CN, 19.0% versus 5.0% for LN) though they had no statistical significance. Patients with hypoechogenic BR had significantly higher HAM-D and HADS-D scores than those with normal BR signal (p = 0.000 for both HAM-D and HADS-D), and most (83.33%) migraineurs with depression exhibited hypoechogenic raphe but none (0.00%) of the migraineurs without depression exhibited hypoechogenic raphe (p = 0.000). CONLUSIONS: TCS signal alteration of BR can be a biomarker for depression in migraine but it is not associated with migraine headache itself. LN and CN alterations in TCS may reflect a potential role of them in the pathogenesis of migraine, which needs to be further elucidated.


Assuntos
Transtorno Depressivo/diagnóstico por imagem , Transtorno Depressivo/patologia , Transtornos de Enxaqueca/diagnóstico por imagem , Transtornos de Enxaqueca/patologia , Núcleos da Rafe/diagnóstico por imagem , Núcleos da Rafe/patologia , Adulto , Estudos de Casos e Controles , Depressão/diagnóstico por imagem , Depressão/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Substância Negra/diagnóstico por imagem , Substância Negra/patologia , Ultrassonografia Doppler Transcraniana , Adulto Jovem
14.
Int J Mol Sci ; 20(9)2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31064126

RESUMO

The current treatments of Parkinson disease (PD) are ineffective mainly due to the poor understanding of the early events causing the decline of dopaminergic neurons (DOPAn). To overcome this problem, slow progressively degenerating models of PD allowing the study of the pre-clinical phase are crucial. We recreated in a short ex vivo time scale (96 h) all the features of human PD (needing dozens of years) by challenging organotypic culture of rat substantia nigra with low doses of rotenone. Thus, taking advantage of the existent knowledge, the model was used to perform a time-dependent comparative study of the principal possible causative molecular mechanisms undergoing DOPAn demise. Alteration in the redox state and inflammation started at 3 h, preceding the reduction in DOPAn number (pre-diagnosis phase). The number of DOPAn declined to levels compatible with diagnosis only at 12 h. The decline was accompanied by a persistent inflammation and redox imbalance. Significant microglia activation, apoptosis, a reduction in dopamine vesicle transporters, and the ubiquitination of misfolded protein clearance pathways were late (96 h, consequential) events. The work suggests inflammation and redox imbalance as simultaneous early mechanisms undergoing DOPAn sufferance, to be targeted for a causative treatment aimed to stop/delay PD.


Assuntos
Neurônios Dopaminérgicos/patologia , Doença de Parkinson/patologia , Substância Negra/patologia , Animais , Células Cultivadas , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Humanos , Estresse Oxidativo , Doença de Parkinson/metabolismo , Ratos , Ratos Wistar , Substância Negra/metabolismo , Técnicas de Cultura de Tecidos/métodos , Ubiquitinação
15.
Br J Radiol ; 92(1101): 20180842, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31067082

RESUMO

A pathological study by Damier et al demonstrated that nigrosome 1, a dopaminergic neuron-rich region in the substantial nigra, is the most severely affected region in idiopathic Parkinson's disease. Since then, researchers have identified the location of nigrosome 1 in the dorsal aspect of the substantia nigra using susceptibility-weighted imaging in MRI. Although this observation was reconfirmed by various imaging techniques and imaging planes, non-standardized imaging methods may rather limit the generalized use of this imaging finding. The aim of this review is to revisit the anatomical definition of the nigrosome 1 region using high-spatial-resolution susceptibility map-weighted MRI in order to help the readers to determine the presence or absence of an abnormality in the nigrosome 1 region. Thereafter, we discuss the current status of nigrosome 1 imaging at 3 T and show how to improve the imaging quality for better assessment of nigrosome 1. We also illustrate the imaging findings of various patients who presented with parkinsonism, which can help the readers to learn how to use these images in practice. Lastly, we discuss potential future works with nigrosome 1 susceptibility map-weighted MRI.


Assuntos
Imagem por Ressonância Magnética/métodos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Substância Negra/diagnóstico por imagem , Substância Negra/patologia , Humanos
16.
Bull Exp Biol Med ; 166(6): 811-815, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31020581

RESUMO

We assessed changes of olfactory bulbs in rata with 6-hydroxydopamine destruction of the substantia nigra. The expression of marker proteins of immature and differentiated neurons and glia (vimentin, PSA-NCAM, tyrosine hydroxylase, and S100) was analyzed by immunohistochemical and morphometric methods. The number of periglomerular dopamine neurons and astroglia in the olfactory bulbs increased on the side of toxin injection and expression of PSA-NCAM and vimentin increased in the rostral migratory stream. Destruction of the substantia nigra shifted differentiation of neuronal progenitors towards the dopaminergic phenotype and increased their survival in the olfactory bulbs, which can be explained by increased expression of PSA-NCAM.


Assuntos
Neuroglia/patologia , Neurônios/patologia , Bulbo Olfatório/patologia , Doença de Parkinson Secundária/patologia , Substância Negra/patologia , Adaptação Fisiológica , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Expressão Gênica , Humanos , Imuno-Histoquímica , Injeções Intraventriculares , Masculino , Atividade Motora/fisiologia , Molécula L1 de Adesão de Célula Nervosa/genética , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Neuroglia/metabolismo , Neurônios/metabolismo , Bulbo Olfatório/metabolismo , Oxidopamina/administração & dosagem , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/genética , Doença de Parkinson Secundária/metabolismo , Ratos , Ratos Wistar , Proteínas S100/genética , Proteínas S100/metabolismo , Ácidos Siálicos/genética , Ácidos Siálicos/metabolismo , Técnicas Estereotáxicas , Substância Negra/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo , Vimentina/genética , Vimentina/metabolismo
17.
Biomed Res Int ; 2019: 6843265, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949504

RESUMO

The aim of this study was to investigate the effect of minocycline in rats with rotenone-induced Parkinson's disease (PD). The open field test was performed to determine the motor ability of the rats. Double immunofluorescence staining was used to detect the expression of tyrosine hydroxylase (TH) and Nurr1 in the substantia nigra (SN) of rats. The relative protein levels of TH, Nurr1, and the total- and phosphorylated-cAMP-response element binding protein (CREB) were determined by western blot analysis. The production of reactive oxygen species (ROS) and nitric oxide (NO) was detected by commercial kits. After exposure to rotenone for 28 days, rats exhibited decreased ambulation and rearing frequency and prolonged immobility time with loss of TH positive neurons in the SN. The phosphorylation levels of CREB and Nurr1 expression decreased significantly accompanied with the release of ROS and NO. Minocycline alleviated the motor deficits of rats lesioned by rotenone and elevated the expression of TH, as well as suppressing the release of ROS and NO in the SN. That was in line with the elevated phosphorylation levels of CREB and Nurr1 expression. In conclusion, our present study showed minocycline protected against neurotoxicity in a rotenone-induced rat model of PD, which was correlated with upregulation of Nurr1.


Assuntos
Minociclina/farmacologia , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/biossíntese , Transtornos Parkinsonianos , Rotenona/administração & dosagem , Substância Negra/metabolismo , Regulação para Cima/efeitos dos fármacos , Animais , Masculino , Óxido Nítrico/metabolismo , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/patologia , Transtornos Parkinsonianos/prevenção & controle , Ratos , Ratos Wistar , Rotenona/farmacologia , Substância Negra/patologia
18.
Eur J Radiol ; 114: 69-75, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31005180

RESUMO

PURPOSE: Mild traumatic brain injury is known to have frequent cognitive impairment. Accumulating evidence is pointing to the malfunctioning of the substantia nigra (SN) as an important factor for head trauma. However, it remains unknown whether changes in the SN-based resting state functional connectivity following mTBI at acute stage and its relationship with cognitive function. MATERIALS AND METHODS: 58 patients with mTBI and 30 age-, gender-, and years of education-matched healthy controls were enrolled in the current study. All of participants received resting state functional magnetic resonance imaging as well as neuropsychological assessment. The resting state functional MR imaging data were analyzed by using a standard seed-based whole-brain correlation method to characterize SN resting state networks. Student t tests were used to perform comparisons. The association between SN resting state networks and performance on neuropsychological measures was also investigated in patients with mTBI by using Pearson rank correlation. RESULTS: Patients with mTBI at acute stage exhibited reduced left SN-based functional connectivity with right insula and caudate and increased left SN-based functional connectivity with left precuneus and left middle occipital gyrus, and reduced right SN-based functional connectivity with left insula. Increased functional connectivity of left precuneus was negatively associated with neurocognitive functions as well (r = -0.266; P = 0.049). CONCLUSION: The present study indicated that patients with acute mTBI suffer from disruption in their SN resting state networks. Moreover, abnormal functional connectivity significantly correlated with cognitive function. Taking together, these results may better improve our understanding of the neuropathological mechanism underlying the neurocognitive symptoms associated with acute mTBI.


Assuntos
Concussão Encefálica/fisiopatologia , Mapeamento Encefálico/métodos , Disfunção Cognitiva/patologia , Imagem por Ressonância Magnética , Substância Negra/patologia , Adulto , Concussão Encefálica/complicações , Concussão Encefálica/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Substância Negra/diagnóstico por imagem
19.
Int J Mol Sci ; 20(7)2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30934738

RESUMO

Parkinson's disease (PD), a multifactorial movement disorder that involves progressive degeneration of the nigrostriatal system affecting the movement ability of the patient. Oxidative stress and neuroinflammation both are shown to be involved in the etiopathogenesis of PD. The aim of this study was to evaluate the therapeutic potential of thymol, a dietary monoterpene phenol in rotenone (ROT)-induced neurodegeneration in rats that precisely mimics PD in humans. Male Wistar rats were injected ROT at a dose of 2.5 mg/kg body weight for 4 weeks, to induce PD. Thymol was co-administered for 4 weeks at a dose of 50 mg/kg body weight, 30 min prior to ROT injection. The markers of dopaminergic neurodegeneration, oxidative stress and inflammation were estimated using biochemical assays, enzyme-linked immunosorbent assay, western blotting and immunocytochemistry. ROT challenge increased the oxidative stress markers, inflammatory enzymes and cytokines as well as caused significant damage to nigrostriatal dopaminergic system of the brain. Thymol treatment in ROT challenged rats appears to significantly attenuate dopaminergic neuronal loss, oxidative stress and inflammation. The present study showed protective effects of thymol in ROT-induced neurotoxicity and neurodegeneration mediated by preservation of endogenous antioxidant defense networks and attenuation of inflammatory mediators including cytokines and enzymes.


Assuntos
Dieta , Neurônios Dopaminérgicos/patologia , Degeneração Neural/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Timol/uso terapêutico , Animais , Catalase/metabolismo , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Glutationa/metabolismo , Mediadores da Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Neostriado/efeitos dos fármacos , Neostriado/patologia , Degeneração Neural/patologia , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos Wistar , Rotenona , Substância Negra/efeitos dos fármacos , Substância Negra/patologia , Superóxido Dismutase/metabolismo , Timol/química , Timol/farmacologia , Tirosina 3-Mono-Oxigenase/metabolismo
20.
Mater Sci Eng C Mater Biol Appl ; 100: 584-597, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30948095

RESUMO

Parkinson's disease (PD) is a long-term neurodegenerative disorders that characterized by a progressive loss of dopaminergic neurons in substantia nigra pars compacta (SNc). Bone marrow stromal cells (BMSCs) are promising therapeutic agents for neurodegenerative disease due to their multipotent capacity. To promote the potential therapeutic effect of BMSCs on PD, we developed an injectable Gelatin-PANI hydrogels as a novel carrier for delivering BMSCs to the SNc region in mice with PD by stereotactic injection. Histology results showed that the BMSCs-loaded hydrogels lead to increased numbers of tyrosine hydroxylase positive (TH+) dopaminergic neurons and fibers in the SNc and striatum, and increased expression of brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in the SNc. Meanwhile, rotarod and open field evaluation demonstrated BMSCs-loaded hydrogels significantly improved the behavioral performance of PD mice. Importantly, BMSCs-loaded hydrogels imparted more sustained protective effects than BMSCs alone in PD mice. Overall, the current data indicate that the hydrogel serves as a promising carrier to deliver BMSCs to the SNc for the treatment of PD.


Assuntos
Portadores de Fármacos/química , Condutividade Elétrica , Gelatina/química , Hidrogéis/química , Injeções , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Doença de Parkinson/terapia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Compostos de Anilina/síntese química , Compostos de Anilina/química , Animais , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Sobrevivência Celular , Preparações de Ação Retardada/farmacologia , Neurônios Dopaminérgicos/patologia , Gelatina/síntese química , Fator Neurotrófico Derivado de Linhagem de Célula Glial/farmacologia , Hidrogéis/síntese química , Masculino , Camundongos Endogâmicos C57BL , Doença de Parkinson/patologia , Reologia , Substância Negra/patologia
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