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1.
Plants (Basel) ; 13(4)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38498455

RESUMO

Chenopodium ambrosioides (L.) is a medicinal and aromatic plant widely used in the Moroccan traditional medicine for its important pharmacological properties. In order to contribute to the valorization of this plant, the current study aimed at evaluating, for the first time, the variation in the yield, chemical composition, and insecticidal and phytotoxic activities of C. ambrosioides essential oil (CAEO) isolated from leaves and inflorescences. The results obtained showed that the CAEO yields vary significantly according to the distilled plant part, with 0.75 ± 0.15% for the leaves and 1.2 ± 0.34% for the inflorescences. CAEO profiling showed quantitative more than qualitative differences. Leaf CAEO was rich in δ-3-carene (61.51%), followed by p-cymene (14.67%) and 1,2:3,4-diepoxy-p-menthane (6.19%). However, inflorescence CAEO was dominated by the same compounds but with variable levels (δ-3-Carene: 44.29%; 1,2:3,4-diepoxy-p-menthane: 19.46%; and p-cymene: 17.85%). The CAEOs from the leaves and inflorescences showed a very interesting inhibiting effect on the germination and growth of the three species used, namely Medicago sativa, Linum rusitatissimum, and Raphanus sativus. However, there was no significant difference between these CAEOs. Similarly, for the insecticidal activity, CAEOs exhibited an important and similar toxicity against Tribolium confusum adults with LD50 of 4.30 and 4.46 µL/L of air and LD90 of 6.51 and 9.62 µL/L air for toxicity by fumigation, while values for contact toxicity on filter paper were 0.04 and 0.05 µL/cm2 for LD50 and 0.08 and 0.09 µL/cm2 for LD90.

2.
Int J Pharm ; 649: 123658, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38042382

RESUMO

Graphene quantum dots (GQDs) are promising biomaterials with potential applicability in several areas due to their many useful and unique features. Among different applications, GQDs are photodynamic therapy agents that generate single oxygen and improve antimicrobial activity. In the present study, and for the first time, GQD were isolated from the Cannabis sativa L. seeds to generate C-GQDs as a new biomaterial for antibacterial and wound healing applications. Detailed characterization was performed using FTIR, UV-vis, Raman spectra, photoluminescence, TEM examination, HRTEM, ζ-potential, and XRD. Our results revealed in vitro and in vivo antibacterial activity of C-GQDs against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) with reduced minimal inhibitory concentration of 236 µg/mL for both strains. In addition, the C-GQDs confirmed the in vitro analysis and exhibited anti-inflammatory activity by reducing the level of neutrophils in blood and skin tissue. C-GQDs act by accelerating re-epithelization and granulation tissue formation. In addition, C-GQDs restored neurobehavioral alteration induced by incisional wounds by reducing oxidative stress, decreasing cortisol levels, increasing anxiolytic-like effect, and increasing vertical locomotor activity. The wound-healing effects of C-GQDs support its role as a potential therapeutic agent for diverse skin injuries.


Assuntos
Cannabis , Grafite , Pontos Quânticos , Animais , Camundongos , Grafite/farmacologia , Escherichia coli , Staphylococcus aureus , Cicatrização , Antibacterianos/farmacologia
3.
Toxicon ; 236: 107345, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37963511

RESUMO

Microcystins (MCs) are cyanobacterial toxins that can negatively impact human and animal health. This study investigated the bioaccumulation, transfer, depuration, and health risks of MCs in strawberry plants (Fragaria vulgaris) and Meriones shawi animals. The plants were irrigated with 1, 5, 10, and 20 µg/L MCs for 60 days (bioaccumulation phase) and then with clean water for 30 days (depuration phase). The harvested plants (roots and leaves) were then prepared in an aliquot form and used as feed for Meriones shawi. Liquid chromatography-mass spectrometry (LC/MS/MS) was used to measure MC concentrations in plant and animal tissues. The bioaccumulation of MCs was found to be highest in the roots, followed by leaves, fruits, liver, stomach, and fecal matter. The bioaccumulation factor (BAF) was highest in perlite (8.48), followed by roots (5.01), leaves (1.55), stomach (0.87), and fecal matter (1.18), indicating that the parts with high bioaccumulation factor had high translocation of MCs. The transfer of MCs to animal organs was low, and the daily toxin intake of adult consumers of strawberry fruit irrigated with 1, 5, 10, and 20 µg/L MC did not exceed the WHO-recommended limit of 0.04 µg MC-LR/Kg of bw/day. However, fruits from plants irrigated with 10 and 20 µg/L may pose a moderate health risk to children (25 Kg bw), and Meriones' consumption of leaves may pose a significant health risk. After the depuration phase, MC concentration in perlite, roots, leaves, and fruits decreased, indicating that depuration reduced the danger of MC transmission and bioaccumulation. The study also found that glutathione reductase and glutathione S-transferase activity were essential in the depuration of MCs in the tested plants. The findings suggest that legislation regulating the quality of irrigation water in terms of MC concentrations is necessary to prevent detrimental consequences to crops and human exposure.


Assuntos
Fragaria , Animais , Criança , Humanos , Gerbillinae , Microcistinas/toxicidade , Microcistinas/análise , Espectrometria de Massas em Tandem , Cadeia Alimentar , Água
4.
Food Chem Toxicol ; 178: 113904, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37356558

RESUMO

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the degeneration of substantia nigra dopaminergic neurons. Many therapeutic strategies were explored for PD with no success. In this study, we investigated the efficacy of graphene oxide nanoparticles (GONPs) using the reserpine model of PD. Low concentrations GONPs were utilized as a therapeutic agent in many neurodegenerative diseases. We assessed the neurobehavioral alterations in the reserpine model of PD and investigated the neuroprotective and antioxidant effects of GONPs in this model. Thirty male mice were separated into three groups (N = 10): C (control); Res (Reserpine 0.25 mg/kg); Res + GONPs (Reserpine 0.25 mg/kg and GONPs 25 mg/kg). Our results showed that reserpine neurotoxicity induced hypoactivity with a significant increase of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels in the brain and brainstem. GONPs reversed the reserpine-induced hypoactivity concomitant with decreased neuronal CAT and MDA levels. These findings support the potential use of GONPs as an antioxidant agent in the central nervous system (CNS) that protects against neurodegeneration in the reserpine PD model.


Assuntos
Doenças Neurodegenerativas , Fármacos Neuroprotetores , Doença de Parkinson , Masculino , Camundongos , Animais , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/etiologia , Reserpina/toxicidade , Reserpina/uso terapêutico , Modelos Animais de Doenças , Estresse Oxidativo , Antioxidantes/metabolismo , Neurônios Dopaminérgicos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
5.
J Trace Elem Med Biol ; 71: 126933, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35066456

RESUMO

BACKGROUND: Lead neurotoxicity is associated with numerous alterations including behavioral and neurochemical disruptions. This study evaluates the possible neurochemical disruption in the subcommissural organ (SCO) after acute (three days) and subchronic (six weeks) Pb-exposure inMeriones shawi, and the possible effect of the third active compound, curcumin-III, in mitigating the neurological alterations caused by lead exposure. METHODS: Using immunohistochemical stainings, we evaluated the Reissner's fiber (RF) secretion utilizing RF-antibody in the SCO. We compared both acute (25 mg/kg bw of Pb i.p. for 3 days) and subchronic (3 g/l of Pb in drinking water for six weeks) Pb-treatedMeriones shawi. RESULTS: The two models of lead exposure showed a significant increase in RF level in the SCO. Conversely, co-treatment with Curcumin-III at a dose of 30 mg/kg bw significantly ameliorate SCO secretory activity, as revealed by decreased RF-immunoreactivity. CONCLUSION: Together, our findings suggest the protective effects of Curcumin-III in regulating the secretory activity of the SCO after Pb-induced neuroanatomical disruptions of the SCO in Meriones.


Assuntos
Curcumina , Órgão Subcomissural , Animais , Chumbo/análise , Imuno-Histoquímica , Gerbillinae , Órgão Subcomissural/química , Órgão Subcomissural/fisiologia , Curcumina/farmacologia
6.
J Chem Neuroanat ; 119: 102055, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34863855

RESUMO

Hepatic encephalopathy (HE) is a neurophysiological syndrome secondary to acute or chronic liver failure. Studies showed that HE patients exhibit a deficit in motor coordination, which may result from cerebellar functional impairment. The aim of this study is to assess the time-dependent alteration of locomotor behavior and the glial and neuronal alteration in rat with acute HE induced chemically. The study was carried out in male Sprague-Dawley rats with thioacetamide (TAA) induced acute liver failure at different stages 12 h, 24 h and 36 h. Hepatic and renal functions were assessed via various biochemical and histopathological examinations, while the cerebellum and the midbrain were examined using histology and immunohistochemistry for tyrosine hydroxylase (TH), cyclooxygenase-2 (COX-2) and glial fibrillary acidic protein (GFAP). We used as well, the open field test and the Rotarod test for assessing the locomotor activity and coordination. Our data showed a progressive loss of liver function and a progressive alteration in locomotor behavior and motor coordination in acute HE rats. In the cerebellum, we noted an increase in the degeneration of cerebellar Purkinje neurons parallel to increased COX-2 immunoreactivity together with astrocytic morphology and density changes. Likewise, in substantia nigra pars compacta, TH levels were reduced. We showed through the current study, a progressive deterioration in locomotor behavior in acute HE rats, as a result of Purkinje neurons death and a deficient dopaminergic neurotransmission, together with the morpho-functional astroglial modifications involving the oxidative stress and neuroinflammation.


Assuntos
Falência Hepática Aguda , Doenças Neuroinflamatórias , Animais , Astrócitos , Cerebelo , Humanos , Falência Hepática Aguda/complicações , Masculino , Ratos , Ratos Sprague-Dawley
7.
Biol Trace Elem Res ; 200(3): 1303-1311, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34176078

RESUMO

At the industrial working conditions, lead exposure could induce several alterations for the human body. Subchronic lead exposure is linked with several injuries including cerebral and renal dysfunctions. The present work discusses the effects of subchronic lead toxicity (3 g/l) in drinking water during the period of treatment (6 weeks) on vasopressin system and epithelial cells in proximal tubules. Also, we aimed to evaluate the protective effect of curcumin-III administered orally by gavage (30 mg/kg BW), against subchronic Pb exposure in Meriones shawi. The biochemical and histopathological examinations demonstrate renal damages induced by lead toxicity. In addition, the behavioral and immunohistochemical studies revealed that Pb neurotoxicity exhibited an anxious behavior with a significant elevation of the vasopressin (AVP) staining within the paraventricular nuclei. The study showed also curcumin-III restored the renal alterations with an anxiolytic effect. Moreover, it restored the AVP level in the studying nuclei. Our work supports a possible link between AVP release and epithelial degeneration in the proximal tubules, and shows a new pharmacological effect of curcumin-III as an anxiolytic agent against lead toxicity.


Assuntos
Curcumina , Animais , Curcumina/farmacologia , Células Epiteliais , Gerbillinae , Humanos , Chumbo/toxicidade , Vasopressinas
8.
J Trace Elem Med Biol ; 65: 126722, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33524682

RESUMO

BACKGROUND: Studies have shown that lead (Pb) is one of hazardous heavy metals with various adverse effects on human health including mental health; Pb can induce psychiatric disorders like anxiety. In the present work, we examined the potential of bisdemethoxycurcumin (BDMC) as a neuroprotective agent against lead induced anxiety inMeriones shawi (M. shawi). METHODS: We asses, the potential of three consecutive day exposure to Pb (25 mg/kg body weight) in inducing anxiogenic effect, serotoninergic and vasopressinergic disruptions inM. shawi. This was done using neurobehavioral tests (open field, elevated plus maze), immunohistochemestry by anti-serotonin (5-HT), and anti-vasopressin (AVP) antibodies. We also measured the possible restorative potential of BDMC (30 mg/kg body weight), delivered by oral gavage. After that, a biochemical and histopathological studies were done. RESULTS: Our results showed that lead exposure for three consecutive days increases significantly the 5-HT-immunoreactivity in dorsal raphe nucleus (DRN) accompanied with a significant enhancement of AVP-immunoreactivity in the cell bodies and fibers in the supraoptic (SON) and paraventricular (PVN) nuclei of the hypothalamus. In the collecting tube, AVP binds to the V2 receptor of the epithelial cells and increases the water permeability. Our results showed clearly the epithelial cells degeneration after lead exposure, then we suggest that the increased AVP could be a response to the hydric balance disrupted after degenerative effect of lead exposure on epithelial cells. BDMC produced an anxiolytic effect in meriones. Moreover, it restored 5-HT and AVP immunoreactivity within studying nuclei. The biochemical and histopathological studies showed that Pb induced renal damages. In addition, BDMC restored the renal alterations. CONCLUSION: According to the obtained results, we suggest new pharmacological effects of BDMC; while it has an anxiolytic effect against Pb-induced anxiety by working on serotoninergic and vasopressinergic systems with an obvious restoration of the renal injuries induced by lead exposure.


Assuntos
Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Diarileptanoides/farmacologia , Rim/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Serotonina/metabolismo , Vasopressinas/metabolismo , Animais , Ansiedade/metabolismo , Diarileptanoides/administração & dosagem , Gerbillinae , Injeções Intraperitoneais , Rim/metabolismo , Rim/patologia , Chumbo/administração & dosagem , Chumbo/toxicidade , Fármacos Neuroprotetores/administração & dosagem
9.
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
10.
Methods Mol Biol ; 2011: 133-142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31273698

RESUMO

Well-functioning of fundamental life processes and human body required metal elements especially essential elements like copper, zinc, magnesium, etc. However, other elements are very toxic for physiological functions including lead (Pb) and cadmium (Cd). Recently, cumulative investigations have interested in the role of metal elements in neurodegenerative diseases and psychiatric disorders especially anxiety and depression. Models of intoxication have been established to evaluate the neurobehavioral effects of metal element exposure via acute and chronic intoxication by metals levels in rats. This method makes available a means to recognize the association between the element level in water, diet, or serum and psychiatric dysfunctions. It allows also to assess the neurobehavioral injuries of metals in animal models and may provide a new window to understand the role metals play in the development of mood and psychiatric disorders.the role metals play in the development of mood and psychiatric disorders.


Assuntos
Transtornos Mentais/etiologia , Metais/efeitos adversos , Doenças do Sistema Nervoso/etiologia , Oligoelementos/efeitos adversos , Doença Aguda , Animais , Comportamento Animal , Biomarcadores , Cádmio , Doença Crônica , Cobre/efeitos adversos , Cobre/metabolismo , Modelos Animais de Doenças , Humanos , Transtornos Mentais/diagnóstico , Transtornos Mentais/metabolismo , Transtornos Mentais/psicologia , Metais/metabolismo , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/fisiopatologia , Fenótipo , Ratos , Avaliação de Sintomas , Oligoelementos/metabolismo , Zinco/efeitos adversos , Zinco/metabolismo
11.
Behav Brain Res ; 367: 201-209, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-30928460

RESUMO

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome resulting from acute or chronic hepatic impairments. The clinical features of HE include attention as well as a mild cognitive deficits associated with impaired attentional and executive networks in patients as well as in animal models of HE. The underlining pathomechanism of memory impairment in HE patients is still not fully understood; however, it may involve a possible gliopathy as well as neuropathy. The aim of the present investigation is to assess progression of short working memory deterioration in acute HE and to delineate the glial and the neuronal alteration which may underlie such cognitive impairment. The study was carried out in male Sprague-Dawley rats with acute liver failure induced by thioacetamide (TAA). The study was performed on different stages of acute HE; 12 h, 24 h and 36 h following administration of TAA. The liver functions were assessed via different biochemical markers (ALT, AST, bilirubin, urea and creatinine) and an histopathological examination of the liver tissue. While for the behavioral study, we used T-Maze test to assess short working memory using the percentage of alternation behavior, together with an immunohistochemical analysis of the Glial Fibrillary Acidic Protein (GFAP) as the key marker of astrocytes in the hippocampus, as well as serotonin (5-HT) for 5-HTergic neurons within the dorsal Raphe nucleus (DRN). Our data revealed a progressive loss of liver tissue integrity with inflammation and hepatocytes degeneration which was associated to obvious loss of the liver function. In parallel, we observed a gradual alteration of the alternation behavior, as a sign of altered short working memory in the acute HE rats. At the central level, the immunohistochemical study showed a time dependent region-specific changes of GFAP-immunoreactive astrocytes within the hippocampus. While within the DRN, serotonin levels declined progressively in a time-dependant manner. Our data revealed for the first time, a gradual loss of short memory function in acute HE, resulting from liver dysfunction. Such cognitive deterioration may involve a possible gliopathy as well as a 5-HTergic dysfunction which could be considered as a new key element for understanding the basis of memory and attention loss in HE patients.


Assuntos
Disfunção Cognitiva/fisiopatologia , Núcleo Dorsal da Rafe , Encefalopatia Hepática/fisiopatologia , Hipocampo , Aprendizagem em Labirinto/fisiologia , Memória de Curto Prazo/fisiologia , Animais , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Modelos Animais de Doenças , Núcleo Dorsal da Rafe/metabolismo , Núcleo Dorsal da Rafe/patologia , Núcleo Dorsal da Rafe/fisiopatologia , Encefalopatia Hepática/complicações , Encefalopatia Hepática/metabolismo , Encefalopatia Hepática/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley
12.
J Chem Neuroanat ; 97: 80-86, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30794879

RESUMO

Metal neurotoxicity is a universal health preoccupation. Previous data revealed an obvious neurochemical impairment induced by metal elements as copper. This investigation was conducted to study the subcommissural organ (SCO) response to acute and subchronic Cu exposure as well as its serotoninergic innervation in Wistar rats, and the probable protective potential of curcumin in these toxicological circumstances. By mean of immunohistochemistry using antibodies against Reissner's fiber (RF) and serotonin (5-HT) in acute model (10 mg/kg i.p. for 3 days) and subchronic model (0.125% in drinking water for six weeks), we noted a significant decrease of RF-immunoreactivity and a whole amplified 5-HT innervation of SCO and ventricular borders in intoxicated rats. Co-treatment with curcumin-I (30 mg/kg B.W) has shown a beneficial effect, reinstating both SCO secretory activity and serotoninergic innervation damaged by Cu exposure. This data revealed for the first time an obvious response of SCO-RF complex to Cu intoxication as well as the neuroprotective effect of curcumin-I. Thus, SCO could play a fundamental role in the strategies of brain resistance to neurotoxicity induced by metal elements in rats, and may be used as biomarker to assist in the diagnosis of this neurotoxicological conditions in rodents.


Assuntos
Cobre/toxicidade , Curcumina/farmacologia , Serotonina/metabolismo , Órgão Subcomissural/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Wistar , Órgão Subcomissural/metabolismo
13.
Acta Histochem ; 121(2): 171-181, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30573341

RESUMO

Lead (Pb) is a metal element released into the atmosphere and a major source of environmental contamination. The accumulation and concentration of this metal in a food web may lead to the intoxication of the body, more precisely, the nervous system (NS). In addition, Pb-exposure can cause structural and functional disruption of the NS. Studies have shown that Pb-exposure could be a risk factor in the development of Parkinson's disease (PD). The latter is related to dopaminergic deficiency that may be triggered by genetic and environmental factors such as Pb intoxication. In this study, we have evaluated, in one hand, the neurotoxic effect of Pb (25 mg / kg B.W i.p) for three consecutive days on dopaminergic system and locomotor performance in Merione shawi. In the other hand, the possible restorative potential of C. sativus (CS) (50 mg / kg BW) by oral gavage. The immunohistochemical approach has revealed that Pb-intoxicated Meriones show a significant increase of Tyrosine Hydroxylase (TH) levels within the Substantia Nigra compacta (SNc), Ventral Tegmental Area (VTA), Locus Coeruleus (LC), Dorsal Striatum (DS) and Medial Forebrain Bundle (MFB), unlike the control meriones, a group intoxicated and treated with Crocus sativus hydroethanolic extract (CSHEE) and treated group by CSHEE. Treatment with CSHEE, has shown a real potential to prevent all Pb-induced damages. In fact, restores the TH levels by 92%, 90%, 88%, 90% and 93% in SNc, VTA, LC, DS and MFB respectively, similarly, locomotor activity dysfunction in Pb-intoxicaed meriones was reinstated by 90%. In this study, we have revealed a new pharmacological potential of Crocus sativus that can be used as a neuroprotective product for neurodegenerative disorders, especially, which implying dopaminergic and noradrenergic injuries, like PD, trigged by heavy metals.


Assuntos
Neurônios Dopaminérgicos/metabolismo , Doença de Parkinson/metabolismo , Parte Compacta da Substância Negra/metabolismo , Área Tegmentar Ventral/metabolismo , Animais , Crocus/metabolismo , Dopamina/metabolismo , Masculino , Feixe Prosencefálico Mediano/metabolismo , Substância Negra/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo
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