RESUMEN
BACKGROUND: Eimeria spp. are coccidian protozoan parasites of domestic and wild animals. Pelecaniform birds are hosts of some Eimeria spp., however, from the family Threskiornithidae only one eimerian species is recorded, Eimeria bazi Chauhan et Bhatia, 1970 which was described from red-naped ibises Pseudibis papillosa (Temminck, 1824) in India. In this study, in turn, this species is morphologically and molecularly identified from buff-necked ibises Theristicus caudatus (Boddaert, 1783) in Brazil. PURPOSE: This study aimed to report E. bazi from buff-necked ibises T. caudatus in southeastern Brazil, revealing the worldwide distribution of this coccidian species, in addition to providing preliminary genotypic identification via sequencing of the mitochondrial cytochrome c oxidase subunit 1 (COI) gene. METHODS: A total of 73 fecal samples were collected from a flock of buff-necked ibises, which remained on the campus of the Federal Rural University of Rio de Janeiro (Universidade Federal Rural do Rio de Janeiro-UFRRJ) from March 2019 to August 2020. Fecal samples were processed by the Sheather's method to recover oocysts. The morphological and morphometrical studies of the oocysts were performed using an optical microscope and graphic editing software. Molecular analysis was performed by sequencing of the COI gene, and the phylogenetic analysis was based in the neighbor-joining and maximum likelihood estimates. RESULTS: Forty-five fecal samples were positive for oocysts identified as E. bazi. This oocysts are ovoidal, 26.2 × 18.9 µm, with smooth to slightly rough wall, c.1.7 µm thick. Micropyle robust and protruding, sometimes with a polar body attached. Oocyst residuum absent, but one or two small polar granules are present. Sporocysts ovoidal to lemon-shaped, 14.2 × 8.7 µm. The Stieda body is knob-like to rounded and sub-Stieda body is absent or vestigial. Sporocyst residuum is composed of granules often membrane-bound. Sporozoites are vermiform, with refractile bodies. This morphology was consistent with the original description of E. bazi from P. papillosa in India. Molecular analysis at the COI gene exhibited low similarity with coccidians sequenced for the same genic region deposited in GenBank, sitting E. bazi separately on the cladogram. CONCLUSIONS: The morphological and molecular studies support the identification of E. bazi from T. caudatus in South America, thus revealing the wide distribution of this eimerian species in the world provided by migratory birds and/or with intercontinental distribution.
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Coccidiosis , Eimeria , Animales , Aves , Brasil , Núcleo Caudado , Coccidiosis/epidemiología , Coccidiosis/parasitología , Coccidiosis/veterinaria , Heces/parasitología , Oocistos , FilogeniaRESUMEN
BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive actions, that presents the involvement of the cortico-striatal areas. The contribution of environmental risk factors to OCD development suggests that epigenetic mechanisms may contribute to its pathophysiology. DNA methylation changes and gene expression were evaluated in post-mortem brain tissues of the cortical (anterior cingulate gyrus and orbitofrontal cortex) and ventral striatum (nucleus accumbens, caudate nucleus and putamen) areas from eight OCD patients and eight matched controls. RESULTS: There were no differentially methylated CpG (cytosine-phosphate-guanine) sites (DMSs) in any brain area, nevertheless gene modules generated from CpG sites and protein-protein-interaction (PPI) showed enriched gene modules for all brain areas between OCD cases and controls. All brain areas but nucleus accumbens presented a predominantly hypomethylation pattern for the differentially methylated regions (DMRs). Although there were common transcriptional factors that targeted these DMRs, their targeted differentially expressed genes were different among all brain areas. The protein-protein interaction network based on methylation and gene expression data reported that all brain areas were enriched for G-protein signaling pathway, immune response, apoptosis and synapse biological processes but each brain area also presented enrichment of specific signaling pathways. Finally, OCD patients and controls did not present significant DNA methylation age differences. CONCLUSIONS: DNA methylation changes in brain areas involved with OCD, especially those involved with genes related to synaptic plasticity and the immune system could mediate the action of genetic and environmental factors associated with OCD.
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Encéfalo/metabolismo , Metilación de ADN , Trastorno Obsesivo Compulsivo/genética , Anciano , Núcleo Caudado , Islas de CpG/genética , Femenino , Giro del Cíngulo , Humanos , Sistema Inmunológico/metabolismo , Inmunidad/genética , Masculino , Plasticidad Neuronal/genética , Núcleo Accumbens , Corteza Prefrontal , PutamenRESUMEN
There is growing evidence suggesting that abnormalities in cortical-basal ganglia circuitry may play a significant role in determining outcomes in schizophrenia. The globus pallidus (GP), a critical structure within this circuitry, unique in its role as a mediator of competing inputs through the striatum, has not been well characterized in schizophrenia. The following study examined functional interactions of the GP in individuals with first-episode schizophrenia (FES). To probe the large-scale intrinsic connectivity of the GP, resting-state fMRI scans were obtained from patients with FES and sex and age-matched healthy controls. Participants with FES were also evaluated after 6 months via the Strauss-Carpenter Outcomes Scale to assess overall functional trajectory. The GP was parcellated to generate seeds within its substructures, and connectivity maps were generated. Our FES cohort showed significantly lower functional connectivity between the left GP interna and a network of regions including the dorsolateral prefrontal cortex, caudate, and cerebellum at baseline. In addition, FES participants with lower overall scores of functioning at 6 months showed significantly decreased connectivity between the GP interna and the dorsal anterior cingulate and bilateral insula, all regions important for motivational salience. These results provide novel evidence for unique abnormalities in functional interactions of the GP with key prefrontal cortical regions in FES. Our findings also suggest that reduced prefrontal-pallidal connectivity may serve as a predictor of early functional outcome.
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Conectoma , Progresión de la Enfermedad , Globo Pálido/fisiopatología , Red Nerviosa/fisiopatología , Corteza Prefrontal/fisiopatología , Trastornos Psicóticos/fisiopatología , Esquizofrenia/fisiopatología , Adolescente , Adulto , Biomarcadores , Núcleo Caudado/diagnóstico por imagen , Núcleo Caudado/fisiopatología , Cerebelo/diagnóstico por imagen , Cerebelo/fisiopatología , Femenino , Estudios de Seguimiento , Globo Pálido/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagen , Corteza Prefrontal/diagnóstico por imagen , Pronóstico , Trastornos Psicóticos/diagnóstico por imagen , Esquizofrenia/diagnóstico por imagen , Adulto JovenRESUMEN
Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessions and/or compulsions. Different striatal subregions belonging to the cortico-striato-thalamic circuitry (CSTC) play an important role in the pathophysiology of OCD. The transcriptomes of 3 separate striatal areas (putamen (PT), caudate nucleus (CN) and accumbens nucleus (NAC)) from postmortem brain tissue were compared between 6 OCD and 8 control cases. In addition to network connectivity deregulation, different biological processes are specific to each striatum region according to the tripartite model of the striatum and contribute in various ways to OCD pathophysiology. Specifically, regulation of neurotransmitter levels and presynaptic processes involved in chemical synaptic transmission were shared between NAC and PT. The Gene Ontology terms cellular response to chemical stimulus, response to external stimulus, response to organic substance, regulation of synaptic plasticity, and modulation of synaptic transmission were shared between CN and PT. Most genes harboring common and/or rare variants previously associated with OCD that were differentially expressed or part of a least preserved coexpression module in our study also suggest striatum subregion specificity. At the transcriptional level, our study supports differences in the 3 circuit CSTC model associated with OCD.
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Núcleo Caudado , Vías Nerviosas/fisiopatología , Núcleo Accumbens , Trastorno Obsesivo Compulsivo/fisiopatología , Putamen , Transcriptoma , Anciano , Anciano de 80 o más Años , Mapeo Encefálico/métodos , Estudios de Casos y Controles , Núcleo Caudado/metabolismo , Núcleo Caudado/fisiopatología , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Masculino , Núcleo Accumbens/metabolismo , Núcleo Accumbens/fisiopatología , Putamen/metabolismo , Putamen/fisiopatologíaRESUMEN
This study aimed to investigate the effect of sulfated polysaccharide from red seaweed Solieria filiformis (Fraction F II) in the inflammatory hypernociception in the temporomandibular joint (TMJ) of rats. Male Wistar rats were pretreated (30min) with a subcutaneous injection (s.c.) of vehicle or FII (0.03, 0.3 or 3.0mg/kg) followed by intra-TMJ injection of 1.5% Formalin or 5-hydroxytryptamine (5-HT, 225µg/TMJ). In other set of experiments rats were pretreated (15min) with an intrathecal injection of the non-selective opioid receptors Naloxone, or µ-opioid receptor antagonist CTOP, or δ-opioid receptor Naltridole hydrochloride, or κ-opioid receptor antagonist Nor-Binaltorphimine (Nor-BNI) followed by injection of FII (s.c.). After 30min, the animals were treated with an intra-TMJ injection of 1.5% formalin. After TMJ treatment, behavioral nociception response was evaluated for a 45-min observation period, animals were terminally anesthetized and periarticular tissue, trigeminal ganglion and subnucleus caudalis (SC) were collected plasma extravasation and ELISA analysis. Pretreatment with F II significantly reduced formalin- and serotonin-induced TMJ nociception, inhibit the plasma extravasation and inflammatory cytokines release induced by 1.5% formalin in the TMJ. Pretreatment with intrathecal injection of Naloxone, CTOP, Naltridole or Nor-BNI blocked the antinociceptive effect of F II in the 1.5% formalin-induced TMJ nociception. In addition, F II was able to significantly increase the ß-endorphin release in the subnucleus caudalis. The results suggest that F II has a potential antinociceptive and anti-inflammatory effect in the TMJ mediated by activation of opioid receptors in the subnucleus caudalis and inhibition of the release of inflammatory mediators in the periarticular tissue.
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Analgésicos Opioides/administración & dosificación , Analgésicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Núcleo Caudado/efectos de los fármacos , Dolor/tratamiento farmacológico , Polisacáridos/uso terapéutico , Articulación Temporomandibular/efectos de los fármacos , Analgésicos Opioides/efectos adversos , Animales , Núcleo Caudado/metabolismo , Interacciones Farmacológicas , Interleucina-1beta/metabolismo , Masculino , Dolor/inducido químicamente , Polisacáridos/química , Ratas , Ratas Wistar , Receptores Opioides/metabolismo , Algas Marinas/inmunología , Sulfatos/química , Articulación Temporomandibular/patología , Factor de Necrosis Tumoral alfa/metabolismo , betaendorfina/metabolismoRESUMEN
PURPOSE: To evaluate whether human immunodeficiency virus (HIV)-positive patients with and without executive functions deficits and healthy control subjects differ on cortical thickness and subcortical brain structures volume in vivo. METHODS: In total, 34 HIV-positive patients with executive functions deficits were compared with 13 HIV-positive patients without executive functions deficits and 19 gender-, age-, and education-matched control subjects. Executive functions impairments were classified by performance on the Wisconsin card sorting test. T1 3-dimensional magnetization prepared rapid gradient echo-weighted imaging was performed using a 1.5 Tesla (magnetic resonance) MR scanner. FreeSurfer software was used to perform cortical reconstruction and volumetric segmentation of subcortical gray matter structures. RESULTS: HIV-positive patients with executive functions deficits had smaller volumes in the right and left caudate compared with the HIV-positive patients without executive functions deficits and control groups. In addition, HIV-positive patients with executive functions deficits had smaller volumes in their left accumbens, right putamen, and globus pallidum compared with the control group. No significant differences in cortical thickness were observed between the groups. CONCLUSION: HIV-positive patients with executive functions deficits have reduced volumes of several subcortical structures, primarily in the caudate nucleus.
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Complejo SIDA Demencia/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Función Ejecutiva/fisiología , Sustancia Gris/diagnóstico por imagen , Seropositividad para VIH/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Complejo SIDA Demencia/patología , Adulto , Anciano , Encéfalo/patología , Brasil , Núcleo Caudado/diagnóstico por imagen , Núcleo Caudado/patología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Femenino , Globo Pálido/diagnóstico por imagen , Globo Pálido/patología , Sustancia Gris/patología , Seropositividad para VIH/patología , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Tamaño de los Órganos , Putamen/diagnóstico por imagen , Putamen/patologíaRESUMEN
BACKGROUND: The discovery of potential disease-modifying therapies in a neurodegenerative condition like Huntington's disease depends on the availability of sensitive biomarkers that reflect decline across disease stages and that are functionally and clinically relevant. AIMS: To quantify macrostructural and microstructural changes in participants with premanifest and symptomatic Huntington's disease over 30 months, and to establish their functional and clinical relevance. METHOD: Multimodal magnetic resonance imaging study measuring changes in macrostructural (volume) and microstructural (diffusivity) measures in 40 patients with premanifest Huntington's disease, 36 patients with symptomatic Huntington's disease and 36 healthy control participants over three testing sessions spanning 30 months. RESULTS: Relative to controls, there was greater longitudinal atrophy in participants with symptomatic Huntington's disease in whole brain, grey matter, caudate and putamen, as well as increased caudate fractional anisotropy; caudate volume loss was the only measure to differ between premanifest Huntington's disease and control groups. Changes in caudate volume and fractional anisotropy correlated with each other and neurocognitive decline; caudate volume loss also correlated with clinical and disease severity. CONCLUSIONS: Caudate neurodegeneration, especially atrophy, may be the most suitable candidate surrogate biomarker for consideration in the development of upcoming clinical trials.
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Núcleo Caudado/patología , Progresión de la Enfermedad , Enfermedad de Huntington/patología , Síntomas Prodrómicos , Adulto , Atrofia , Biomarcadores , Núcleo Caudado/diagnóstico por imagen , Femenino , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Humanos , Enfermedad de Huntington/diagnóstico por imagen , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Imagen Multimodal , Putamen/diagnóstico por imagen , Putamen/patologíaRESUMEN
BACKGROUND AND PURPOSE: Amyotrophic Lateral Sclerosis (ALS) is characterized by extensive corticospinal damage, but extrapyramidal involvement is suggested in pathological studies. Texture analysis (TA) is an image processing technique that evaluates the distribution of gray levels between pixels in a given region of interest (ROI). It provides quantitative data and has been employed in several neurodegenerative disorders. Here, we used TA to investigate possible deep gray nuclei (DGN) abnormalities in a cohort of ALS patients. METHODS: Thirty-two ALS patients and 32 healthy controls underwent MRI in a 3T scanner. The T1 volumetric sequence was used for DGN segmentation and extraction of 11 texture parameters using the MaZda software. Statistical analyses were performed using the Mann-Whitney non-parametric test, with a significance level set at α = 0.025 (FDR-corrected) for TA. RESULTS: Patients had significantly higher values for the parameter correlation (CO) in both thalami and in the right caudate nucleus compared to healthy controls. Also, the parameter Inverse Difference Moment or Homogeneity (IDM) presented significantly smaller values in the ALS group in both thalami. CONCLUSIONS: TA of T1 weighted images revealed DGN alterations in patients with ALS, namely in the thalami and caudate nuclei.
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Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Núcleo Caudado/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Tálamo/diagnóstico por imagen , Adulto , Anciano , Esclerosis Amiotrófica Lateral/patología , Núcleo Caudado/patología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Tálamo/patologíaRESUMEN
BACKGROUND: Psychosis prevalence in Parkinson's disease is estimated at 8-30%. Proton magnetic resonance spectroscopy measures specific metabolites as markers of cell functioning. OBJECTIVE: To study N-acetyl-aspartate and glutamate levels in the caudate and putamen nuclei in subjects with Parkinson's disease with and without psychosis. METHODS: We included 20 non-demented Parkinson's disease patients with psychosis and 20 Parkinson's disease patients without psychosis matched for age, sex, disease duration, and levodopa equivalent daily dose, all attended at an academic medical center. Proton magnetic resonance spectroscopy scans were performed in a 3T GE whole-body scanner. RESULTS: Decreased glutamate levels scaled to creatine were found in the dorsal caudate (p = 0.005) and putamen (p = 0.007) of the Parkinson's disease psychosis group compared with the without psychosis group. Glutamate plus glutamine levels scaled to creatine and N-acetyl-aspartate levels scaled to creatine were also significantly reduced in the dorsal caudate of the Parkinson's disease with psychosis group (p = 0.018 and p = 0.011, respectively). No group differences were found for any of the other metabolites in the two regions of interest. CONCLUSIONS: Our findings suggest that decreased metabolite levels in specific brain areas may be implicated in the development of psychosis in Parkinson's disease.
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Antiparkinsonianos/uso terapéutico , Enfermedad de Parkinson/psicología , Espectroscopía de Protones por Resonancia Magnética/métodos , Trastornos Psicóticos/diagnóstico , Centros Médicos Académicos , Anciano , Antiparkinsonianos/administración & dosificación , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Encéfalo/metabolismo , Encéfalo/patología , Núcleo Caudado/metabolismo , Femenino , Ácido Glutámico/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/tratamiento farmacológico , Trastornos Psicóticos/etiología , Putamen/metabolismoRESUMEN
Manganese (Mn) is able to cross the blood-brain barrier and induces functional and structural alterations during the intoxication by this metal. Therefore, the effects of chronic administration of Mn in the caudate nucleus of mice were evaluated by electron microscopy. Male albino mice were injected intraperitoneally with MnCl2 (5 mg/kg/d) 5 d per week during 9 weeks. The control group received only 0.9% of NaCl solution. The caudate nuclei were extracted and subsequently processed to be observed on a conventional transmission electron microscope at 2, 4, 6, and 9 weeks after treatment. A high percentage of vacuolated and swollen mitochondria were found throughout all the analyzed periods. Myelin disarrangement and ultrastructural alterations related to edema were observed increased in Mn-treated mice at week 9. Granular degeneration of myelin at week 9 accompanied with deposition of electron dense granules in the neuropil was also observed. Edema in neuropil and glial cells was detected from week 2 to week 9 accompanied by swollen mitochondria. Neuronal bodies, synaptic terminals, and perivascular cells were found swollen. Decreased electron density in postsynaptic areas and decreased and dispersed synaptic vesicles in presynaptic areas were noted in Mn-treated animals. Some neurons from Mn-treated mice showed cisternae dilation of the Golgi apparatus. These results suggest that Mn-treatment produces structural alterations in the caudate nucleus that could be responsible for some of the neurotoxic effects of this metal.
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Núcleo Caudado/ultraestructura , Cloruros/toxicidad , Vaina de Mielina/ultraestructura , Fibras Nerviosas Mielínicas/ultraestructura , Animales , Núcleo Caudado/efectos de los fármacos , Masculino , Compuestos de Manganeso , Ratones , Microscopía Electrónica de Transmisión , Mitocondrias/efectos de los fármacos , Mitocondrias/ultraestructura , Vaina de Mielina/efectos de los fármacos , Fibras Nerviosas Mielínicas/efectos de los fármacos , Espectrofotometría AtómicaRESUMEN
BACKGROUND: Depression is a prevalent disorder that significantly affects the social functioning and interpersonal relationships of individuals. This highlights the need for investigation of the neural mechanisms underlying these social difficulties. Investigation of social exchanges has traditionally been challenging as such interactions are difficult to quantify. Recently, however, neuroeconomic approaches that combine multiplayer behavioural economic paradigms and neuroimaging have provided a framework to operationalize and quantify the study of social interactions and the associated neural substrates. METHOD: We investigated brain activation using functional magnetic resonance imaging (fMRI) in unmedicated depressed participants (n = 25) and matched healthy controls (n = 25). During scanning, participants played a behavioural economic paradigm, the Ultimatum Game (UG). In this task, participants accept or reject monetary offers from other players. RESULTS: In comparison to controls, depressed participants reported decreased levels of happiness in response to 'fair' offers. With increasing fairness of offers, controls activated the nucleus accumbens and the dorsal caudate, regions that have been reported to process social information and responses to rewards. By contrast, participants with depression failed to activate these regions with increasing fairness, with the lack of nucleus accumbens activation correlating with increased anhedonia symptoms. Depressed participants also showed a diminished response to increasing unfairness of offers in the medial occipital lobe. CONCLUSIONS: Our findings suggest that depressed individuals differ from healthy controls in the neural substrates involved with processing social information. In depression, the nucleus accumbens and dorsal caudate may underlie abnormalities in processing information linked to the fairness and rewarding aspects of other people's decisions.
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Núcleo Caudado/fisiopatología , Trastorno Depresivo/fisiopatología , Relaciones Interpersonales , Principios Morales , Núcleo Accumbens/fisiopatología , Adulto , Anhedonia/fisiología , Femenino , Juegos Experimentales , Humanos , Imagen por Resonancia Magnética , Masculino , Recompensa , Adulto JovenRESUMEN
Area V4 has numerous, topographically organized connections with multiple cortical areas, some of which are important for spatially organized visual processing, and others which seem important for spatial attention. Although the topographic organization of V4's connections with other cortical areas has been established, the detailed topography of its connections with subcortical areas is unclear. We therefore injected retrograde and anterograde tracers in different topographical regions of V4 in nine macaques to determine the organization of its subcortical connections. The injection sites included representations ranging from the fovea to far peripheral eccentricities in both the upper and lower visual fields. The topographically organized connections of V4 included bidirectional connections with four subdivisions of the pulvinar, two subdivisions of the claustrum, and the interlaminar portions of the lateral geniculate nucleus, and efferent projections to the superficial and intermediate layers of the superior colliculus, the thalamic reticular nucleus, and the caudate nucleus. All of these structures have a possible role in spatial attention. The nontopographic, or converging, connections included bidirectional connections with the lateral nucleus of the amygdala, afferent inputs from the dorsal raphe, median raphe, locus coeruleus, ventral tegmentum and nucleus basalis of Meynert, and efferent projections to the putamen. Any role of these structures in attention may be less spatially specific.
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Corteza Visual/química , Corteza Visual/fisiología , Vías Visuales/química , Vías Visuales/fisiología , Amígdala del Cerebelo/química , Amígdala del Cerebelo/fisiología , Animales , Atención/fisiología , Núcleo Caudado/química , Núcleo Caudado/fisiología , Macaca , Macaca mulatta , Colículos Superiores/química , Colículos Superiores/fisiologíaRESUMEN
Social Anxiety Disorder (SAD) is more common among PD patients than in the general population. This association may be explained by psychosocial mechanisms but it is also possible that neurobiological mechanism underlying PD can predispose to SAD. The aim of this study was to investigate a possible dopaminergic mechanism involved in PD patients with SAD, by correlating striatal dopamine transporter binding potential (DAT-BP) with intensity of social anxiety symptoms in PD patients using SPECT with TRODAT-1 as the radiopharmaceutical. Eleven PD patients with generalized SAD and 21 PD patients without SAD were included in this study; groups were matched for age, gender, disease duration and disease severity. SAD diagnosis was determined according to DSM IV criteria assessed with SCID-I and social anxiety symptom severity with the Brief Social Phobia Scale (BSPS). Demographic and clinical data were also collected. DAT-BP was significantly correlated to scores on BSPS for right putamen (r=0.37, p=0.04), left putamen (r=0.43, p=0.02) and left caudate (r=0.39, p=0.03). No significant correlation was found for the right caudate (r=0.23, p=0.21). This finding may reinforce the hypothesis that dopaminergic dysfunction might be implicated in the pathogenesis of social anxiety in PD.
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Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Enfermedad de Parkinson/metabolismo , Trastornos Fóbicos/metabolismo , Adulto , Anciano , Núcleo Caudado/diagnóstico por imagen , Estudios Transversales , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Compuestos de Organotecnecio , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Trastornos Fóbicos/complicaciones , Trastornos Fóbicos/diagnóstico por imagen , Unión Proteica , Escalas de Valoración Psiquiátrica , Putamen/diagnóstico por imagen , Radiofármacos , Tomografía Computarizada de Emisión de Fotón Único , TropanosRESUMEN
The glutamatergic and dopaminergic systems are thought to be involved in the pathophysiology of schizophrenia. Their interaction has been widely documented and may have a role in the neurobiological basis of the disease. The aim of this study was to compare, using proton magnetic resonance spectroscopy ((1)H-MRS), glutamate levels in the precommissural dorsal-caudate (a dopamine-rich region) and the cerebellar cortex (negligible for dopamine) in the following: (1) 18 antipsychotic-naïve subjects with prodromal symptoms and considered to be at ultra high-risk for schizophrenia (UHR), (2) 18 antipsychotic-naïve first- episode psychosis patients (FEP), and (3) 40 age- and sex- matched healthy controls. All subjects underwent a (1)H-MRS study using a 3Tesla scanner. Glutamate levels were quantified and corrected for the proportion of cerebrospinal fluid and percentage of gray matter in the voxel. The UHR and FEP groups showed higher levels of glutamate than controls, without differences between UHR and FEP. In the cerebellum, no differences were seen between the three groups. The higher glutamate level in the precommissural dorsal-caudate and not in the cerebellum of UHR and FEP suggests that a high glutamate level (a) precedes the onset of schizophrenia, and (b) is present in a dopamine-rich region previously implicated in the pathophysiology of schizophrenia.
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Núcleo Caudado/metabolismo , Ácido Glutámico/metabolismo , Trastornos Psicóticos/metabolismo , Esquizofrenia/metabolismo , Adolescente , Adulto , Edad de Inicio , Núcleo Caudado/patología , Núcleo Caudado/fisiopatología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/fisiopatología , Factores de Riesgo , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatología , Regulación hacia Arriba/fisiología , Adulto JovenRESUMEN
OBJECTIVES: To evaluate patients with "clinically established" psychogenic parkinsonism (PsyP) using single-photon emission computer tomography (SPECT) with the technetium-99m labeled tracer TRODAT-1, a dopamine transporter (DAT) ligand, and investigate whether these patients have an underlying degenerative parkinsonism. PATIENTS AND METHODS: Five patients with PsyP were assessed using demographic data, standard clinical scales for Parkinson's Disease (PD), and a neuropsychiatric interview. DAT imaging using SPECT with TRODAT-1 was performed, and values for caudate/putamen DAT binding potentials (BP) registered. Patients with PsyP were matched with PD (n=5) and healthy control subjects (n=5). RESULTS: The mean age (years-old) at first evaluation in the PsyP group was 37.4+/-3.7, and the mean disease duration (years) was 3.9+/-1.2. DAT BPs (means+/-standard deviations) on right/left caudate were, respectively, 0.69+/-0.18 and 0.70+/-0.18 in the PD group versus 1.17+/-0.06 and 1.12+/-0.10 in the control group. DAT BPs on right/left putamen were, respectively, 0.48+/-0.10 and 0.45+/-0.06 in the PD group versus 1.10+/-0.10 and 1.21+/-0.43 in the control group. Two out of five patients from the PsyP group had values for DAT BP in the putamen under the cut-off (< or =0.70) for controls, implying pre-synaptic dopaminergic deficit. CONCLUSIONS: Our data in this small group of patients suggest that DAT imaging is a tool that may help in the identification of underlying degenerative parkinsonism in PsyP.
Asunto(s)
Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Enfermedades Neurodegenerativas/diagnóstico por imagen , Enfermedades Neurodegenerativas/patología , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/patología , Adulto , Núcleo Caudado/diagnóstico por imagen , Femenino , Humanos , Masculino , Enfermedades Neurodegenerativas/metabolismo , Compuestos de Organotecnecio , Enfermedad de Parkinson/metabolismo , Putamen/diagnóstico por imagen , Radiofármacos , Factores Socioeconómicos , Tomografía Computarizada de Emisión de Fotón Único , Resultado del Tratamiento , TropanosRESUMEN
The development of sensitization to the locomotor effects of morphine and cross-sensitization between morphine and cocaine were evaluated in adult rats submitted to a protein malnutrition schedule from the 14th day of gestation up to 30 days of age (D-rats), and compared with well-nourished animals (C-rats). Dose-response curves to morphine-induced locomotor activity (5, 7.5, 10 or 15 mg/kg, i.p., every other day for 5 days) revealed a shift to the left in D-rats compared to C-rats. This implies that D-rats showed behavioral sensitization to the lower dose of morphine used (5 mg/kg), which was ineffective in C-rats. Furthermore, when a cocaine challenge (10 mg/kg, i.p) was given 48 h after the last morphine administration, only D-rats exhibited cross-sensitization in morphine-pretreated animals (7.5 and 10 mg/kg). In order to correlate the differential response observed with the functioning of the mesocorticolimbic dopaminergic system, extracellular dopamine (DA) levels were measured in the nucleus accumbens (core and shell) and the dorsal caudate-putamen. A challenge with cocaine in morphine pre-exposed animals produced an increase in DA release, but only in the nucleus accumbens "core" of D-rats. Similar DA levels were found in the nucleus accumbens "shell" and in the dorsal caudate-putamen of both groups. Finally, these results demonstrate that D-rats had a lower threshold for developing both a progressive behavioral sensitization to morphine and a cross-sensitization to cocaine. In accordance with these behavioral findings, a higher responsiveness of the nucleus accumbens core, expressed by increased DA levels, both basal and after cocaine challenge, was observed in D-rats.
Asunto(s)
Cocaína/farmacología , Inhibidores de Captación de Dopamina/farmacología , Locomoción/efectos de los fármacos , Desnutrición/fisiopatología , Morfina/farmacología , Narcóticos/farmacología , Envejecimiento , Animales , Núcleo Caudado/efectos de los fármacos , Núcleo Caudado/fisiopatología , Cocaína/administración & dosificación , Cocaína/sangre , Dopamina/metabolismo , Inhibidores de Captación de Dopamina/administración & dosificación , Inhibidores de Captación de Dopamina/sangre , Relación Dosis-Respuesta a Droga , Femenino , Locomoción/fisiología , Masculino , Morfina/administración & dosificación , Morfina/sangre , Narcóticos/administración & dosificación , Narcóticos/sangre , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/fisiopatología , Embarazo , Efectos Tardíos de la Exposición Prenatal , Putamen/efectos de los fármacos , Putamen/fisiopatología , Ratas , Ratas WistarRESUMEN
OBJECTIVE: To compare glutamate levels (Glu) found in the dorsal-caudate nucleus (a dopamine rich region) and in the cerebellum (a low dopamine region) among: 1) schizophrenia patients undergoing an acute psychotic episode, 2) after receiving antidopaminergic treatment (Risperidone), and 3) healthy controls. METHODS: Fourteen drug-free patients with schizophrenia and fourteen healthy controls were included. Patients underwent two proton magnetic resonance spectroscopy (1H-MRS) studies, one prior to treatment and the second after 6-weeks of daily Risperidone treatment. Controls underwent one 1H-MRS study. Glutamate levels were normalized according to the relative concentration of Creatine (Cr). RESULTS: The dorsal-caudate nucleus among schizophrenia patients showed higher levels of Glu/Cr during the drug-free condition (t = -2.16, p = 0.03) and after antipsychotic treatment (t = 2.12, p = 0.04) compared with controls. No difference was observed in the cerebellum between the drug-free, post-treatment and controls conditions. CONCLUSIONS: Our results suggest that the Glu increase observed in the dorsal-caudate in schizophrenia is illness-mediated and does not change after 6-weeks of antipsychotic treatment. Moreover, the lack of change detected in the cerebellum suggests that the Glu increase in schizophrenia is not ubiquitous within the brain and that may be associated with dopamine target regions.
Asunto(s)
Núcleo Caudado/química , Cerebelo/química , Ácido Glutámico/análisis , Espectroscopía de Resonancia Magnética , Esquizofrenia/metabolismo , Adulto , Femenino , Humanos , Estudios Longitudinales , Masculino , Adulto JovenRESUMEN
Objetivo: Comparar los niveles de glutamato en el núcleo caudado dorsal, región rica en dopamina, y el cerebelo, región pobre en dopamina, en pacientes con esquizofrenia, durante un episodio psicótico agudo, después de recibir tratamiento antidopaminérgico (risperidona) y en controles sanos. Métodos: Se incluyeron 14 pacientes con esquizofrenia aguda sin tratamiento y 14 controles sanos. A los pacientes se les realizaron dos estudios de espectroscopia por resonancia magnética de protones (ERM1H). El primero antes de tratamiento y el segundo a las seis semanas de tratamiento efectivo. Los controles fueron evaluados en una ocasión. Los niveles de glutamato fueron normalizados con la concentración de creatina. Resultados: Los niveles de glutamato/creatina fueron mayores en el caudado dorsal de los pacientes previo a tratamiento (t=-2.16, p=0.03) y después del tratamiento en comparación con los controles (t=2.12, p=0.04). Los niveles de glutamato en el cerebelo no cambiaron con el tratamiento y fueron iguales a los controles. Conclusiones: Nuestros resultados indican que el incremento delglutamato en el caudado dorsal se encuentra en relación con la enfermedad y no cambia después de seis semanas de tratamiento antipsicótico efectivo. Más aún, la ausencia de diferencias en el cerebelo sugiere que el incremento del glutamato presente en la esquizofrenia se podría relacionar a regiones con abundante inervación dopaminérgica.
OBJECTIVE: To compare glutamate levels (Glu) found in the dorsal-caudate nucleus (a dopamine rich region) and in the cerebellum (a low dopamine region) among: 1) schizophrenia patients undergoing an acute psychotic episode, 2) after receiving antidopaminergic treatment (Risperidone), and 3) healthy controls. METHODS: Fourteen drug-free patients with schizophrenia and fourteen healthy controls were included. Patients underwent two proton magnetic resonance spectroscopy (1H-MRS) studies, one prior to treatment and the second after 6-weeks of daily Risperidone treatment. Controls underwent one 1H-MRS study. Glutamate levels were normalized according to the relative concentration of Creatine (Cr). RESULTS: The dorsal-caudate nucleus among schizophrenia patients showed higher levels of Glu/Cr during the drug-free condition (t = -2.16, p = 0.03) and after antipsychotic treatment (t = 2.12, p = 0.04) compared with controls. No difference was observed in the cerebellum between the drug-free, post-treatment and controls conditions. CONCLUSIONS: Our results suggest that the Glu increase observed in the dorsal-caudate in schizophrenia is illness-mediated and does not change after 6-weeks of antipsychotic treatment. Moreover, the lack of change detected in the cerebellum suggests that the Glu increase in schizophrenia is not ubiquitous within the brain and that may be associated with dopamine target regions.
Asunto(s)
Humanos , Masculino , Femenino , Adulto Joven , Ácido Glutámico/análisis , Cerebelo/química , Esquizofrenia/metabolismo , Espectroscopía de Resonancia Magnética , Núcleo Caudado/química , Estudios LongitudinalesRESUMEN
RATIONALE: Higher doses of benzodiazepines induce sedation. However, in low to moderate doses, benzodiazepines can increase aggressive behavior both after acute and chronic administration. The determinants for increasing aggression after chronic intake of flunitrazepam, a so-called date rape drug, in violence-prone individuals are incompletely understood. OBJECTIVES: The aim of this study is to assess the effects of acute and chronic treatment with flunitrazepam on male aggression in resident rats. We also examined possible changes in binding to benzodiazepine receptors throughout the brain of rats that display aggressive behavior after repeated flunitrazepam treatment using quantitative receptor autoradiography. MATERIALS AND METHODS: The behaviors of the male Wistar resident rats (n = 35) toward a male intruder were recorded for 10 min twice a week. The salient aggressive and non-aggressive elements in the resident rat's behavior were analyzed. Initially, the dose-dependent effects of flunitrazepam (0.01, 0.03, 0.1, 0.18, and 0.3 mg/kg) or vehicle were determined in all rats; subsequently, 0.3 mg/kg per day flunitrazepam was administered for 42 days (n = 15), and a parallel group was treated with vehicle (n = 20). After the chronic treatment, the flunitrazepam (0, 0.01, 0.03, 0.1, 0.18, and 0.3 mg/kg) effects were again assessed. RESULTS: The most significant finding is the escalation of aggression after chronic treatment with flunitrazepam. A previously sedative 0.3 mg/kg dose of flunitrazepam engendered very high levels of attack bites, sideways threats, and aggressive postures (total aggression) after 6 weeks of daily administration. Individual differences emerged, and these were associated with decreased binding to benzodiazepine receptors, mainly in the limbic structures such as the cingulate cortex (cingulate areas 1 and 2) and caudate-putamen (posterior part) of aggressive animals, suggesting that these areas are pivotal in the control of emotional and aggressive behavior. CONCLUSIONS: Chronic flunitrazepam produces changes in receptor binding in discrete areas of the cingulate cortex and caudate-putamen that are proposed to be part of the mechanisms for increased expression of aggressive behavior.
Asunto(s)
Agresión/efectos de los fármacos , Agresión/psicología , Núcleo Caudado/metabolismo , Corteza Cerebral/metabolismo , Flunitrazepam/metabolismo , Flunitrazepam/farmacología , Moduladores del GABA/metabolismo , Moduladores del GABA/farmacología , Putamen/metabolismo , Receptores de GABA-A/metabolismo , Animales , Autorradiografía , Conducta Animal/efectos de los fármacos , Sitios de Unión , Núcleo Caudado/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Individualidad , Masculino , Putamen/efectos de los fármacos , Ratas , Receptores de GABA-A/efectos de los fármacosRESUMEN
Acute and repeated psychostimulant administration induces a long-lasting enhanced behavioural response to a subsequent drug challenge, known as behavioural sensitization. This phenomenon involves persistent neurophysiological adaptations, which may lead to drug addiction. Brain dopaminergic pathways have been implicated as the main neurobiological substrates of behavioural sensitization, although other neurotransmitters and neuromodulators may also participate. In order to investigate a possible involvement of opioid systems in amphetamine (AMPH) behavioural sensitization, we studied the AMPH-induced changes in Proenkephalin (Pro-Enk) mRNA expression in forebrain areas in both drug-naïve and AMPH-sensitized rats. Male Sprague-Dawley rats were sensitized to AMPH by means of a single AMPH (1 mg/kg s.c.) injection and the same dose was injected 7 days later to assess the expression of sensitization. Pro-Enk mRNA levels were evaluated by in situ hybridization in coronal brain sections. AMPH injection induced an increase in Pro-Enk mRNA expression in the nucleus accumbens and the medial-posterior caudate-putamen in drug-naïve rats. Challenge with AMPH to rats injected 1 week earlier with AMPH induced motor sensitization and increased and decreased Pro-Enk mRNA expression in the prefrontal cortex and the anterior medial caudate-putamen, respectively. Our results suggest that alterations in cortical and striatal enkephalinergic systems could contribute to the expression of AMPH behavioural sensitization.