Asunto(s)
Ablación por Catéter/métodos , Procedimientos Neuroquirúrgicos/métodos , Enfermedad de Parkinson/cirugía , Núcleo Subtalámico/cirugía , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paresia/etiología , Enfermedad de Parkinson/fisiopatología , Resultado del TratamientoRESUMEN
OBJECTIVE: Subthalamotomy is an effective alternative for the treatment of Parkinson's disease (PD). However, uncertainty about the optimal target location and the possibility of inducing haemichorea-ballism have limited its application. We assessed the correlation between the topography of radiofrequency-based lesions of the subthalamic nucleus (STN) with motor improvement and the emergence of haemichorea-ballism. METHODS: Sixty-four patients with PD treated with subthalamotomy were evaluated preoperatively and postoperatively using the Unified Parkinson's Disease Rating Scale motor score (UPDRSm), MRI and tractography. Patients were classified according to the degree of clinical motor improvement and dyskinesia scale. Lesions were segmented on MRI and averaged in a standard space. We examined the relationship between the extent of lesion-induced disruption of fibres surrounding the STN and the development of haemichorea-ballism. RESULTS: Maximum antiparkinsonian effect was obtained with lesions located within the dorsolateral motor region of the STN as compared with those centre-placed in the dorsal border of the STN and the zona incerta (71.3%, 53.5% and 20.8% UPDRSm reduction, respectively). However, lesions that extended dorsally beyond the STN showed lower probability of causing haemichorea-ballism than those placed entirely within the nucleus. Tractography findings indicate that interruption of pallidothalamic fibres probably determines a low probability of haemichorea-ballism postoperatively. CONCLUSIONS: The topography of the lesion is a major factor in the antiparkinsonian effect of subthalamotomy in patients with PD. Lesions involving the motor STN and pallidothalamic fibres induced significant motor improvement and were associated with a low incidence of haemichorea-ballism.
Asunto(s)
Técnicas de Ablación , Discinesias/terapia , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/cirugía , Núcleo Subtalámico/cirugía , Anciano , Discinesias/diagnóstico , Discinesias/epidemiología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , Recuperación de la Función , Núcleo Subtalámico/diagnóstico por imagen , Resultado del TratamientoRESUMEN
Unilateral subthalamotomy is an effective treatment for the cardinal motor features of Parkinson's disease (PD). However, non-motor changes possibly associated with right or left subthalamotomy remain unknown. Our aim was to assess cognitive, psychiatric and neuroimaging changes after treatment with unilateral subthalamotomy. Fourteen medicated patients with PD were evaluated before and after (mean 6 months after operation) unilateral subthalamotomy (5 right, 9 left). In addition to motor assessments, cognitive (global cognition and executive functions), psychiatric (apathy, depression, anxiety, mania, hypo- and hyperdopaminergic behaviours, impulsivity), quality of life evaluations and volume of lesions were obtained. After surgery, significant improvement of motor signs was observed. Unilateral subthalamotomy improved general cognitive status, but left subthalamotomy reduced semantic verbal fluency compared to the pre-operative state. Depression and quality of life were improved with both right and left subthalamotomy. However, hyper-emotionality was present after surgery and right subthalamotomy increased impulsivity and disinhibition (on NeuroPsychiatric Inventory and Ardouin Scale for Behaviour in PD), a result linked to larger lesion volumes. We conclude that unilateral subthalamotomy is effective for treating the cardinal motor features of PD and improves mood. Right subthalamotomy is associated with greater risk of impulsivity and disinhibition, while left subthalamotomy induces further impairment of semantic verbal fluency.
Asunto(s)
Cognición/fisiología , Enfermedad de Parkinson/cirugía , Calidad de Vida/psicología , Núcleo Subtalámico/cirugía , Adulto , Ansiedad/diagnóstico por imagen , Ansiedad/psicología , Apatía/fisiología , Depresión/diagnóstico por imagen , Depresión/psicología , Función Ejecutiva/fisiología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neuroimagen , Pruebas Neuropsicológicas , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/psicología , Núcleo Subtalámico/diagnóstico por imagen , Resultado del TratamientoRESUMEN
A escala mundial, la isquemia cerebral constituye una de las principales causas de muerte, por lo que los modelos animales de isquemia cerebral son extensamente usados tanto en el estudio de la pato-fisiología del fenómeno isquémico; como en la evaluación de agentes terapéuticos con posible efecto protector o regenerador. Los objetivos de este estudio fueron examinar la presencia de daño neuronal en diferentes áreas cerebrales como consecuencia del evento isquémico; así como evaluar consecuencias de este proceder sobre los procesos de memoria-aprendizaje. Los grupos de estudios incluyeron un grupo experimental de animales isquémicos, 30 ratas a las que se les ocluyó ambas arterias carótidas comunes, y un grupo control. Fue evaluada la expresión de genes isquémicos e inflamatorios por técnicas de qPCR 24 horas post lesión, la morfología del tejido cerebral en áreas de corteza, estriado e hipocampo, siete días post lesión y los procesos de memoria y aprendizaje, 12 días post lesión. Los estudios morfológicos evidenciaron que el proceder induce la muerte de poblaciones celulares en corteza, estriado e hipocampo; la isquemia modificó la expresión los genes gfap, ho-1, il-6, il-17 e ifn-γ, lo cual puede ser utilizado como un marcador de proceso isquémico temprano. Adicionalmente, el daño isquémico causó un deterioro en la memoria espacial. Esta caracterización nos permite contar con un modelo experimental donde desarrollar futuros estudios sobre la patofisiología de los eventos isquémicos y la evaluación de estrategias terapéuticas.
Cerebral ischemia is a major cause of death, for this reason animal models of cerebral ischemia are widely used to study both the pathophysiology of ischemic phenomenon and the evaluation of possible therapeutic agents with protective or regenerative properties. The objectives of this study were to examine the presence of neuronal damage in different brain areas following the ischemic event, and assess consequences of such activities on the processes of memory and learning. The study group included an experimental group ischemic animals (30 rats with permanent bilateral occlusion of the carotids), and a control group. Was evaluated gene expression and inflammatory ischemic by qPCR techniques 24h post injury, brain tissue morphology in areas of cortex, striatum and hippocampus seven days post injury and processes of memory and learning, 12 days post injury. The morphological studies showed that the procedure induces death of cell populations in cortex, striatum and hippocampus, ischemia modified gfap gene expression and ho, il-6, il-17 and ifn-γ, which can be used as a marker of early ischemic process. Additionally, the ischemic injury caused spatial memory decline. This characterization gives us an experimental model to develop future studies on the pathophysiology of ischemic events and assessing therapeutic strategies.
RESUMEN
Glutathione is the major antioxidant in the living cells. Its deficit has been linked to neurodegenerative disorders as Parkinson's disease but its role in the etiology of nigral degeneration and sensory-motor performance has been poorly explored. To evaluate the effect of glutathione depletion on nigro-striatal oxidative metabolism and sensory-motor performance in rats, l-buthionine sulfoximine (15 mM) or saline solution was injected into substantia nigra pars compacta (SNpc). Then, oxidative metabolism was studied 24h and 7 days later in SNpc and corpus striatum (CS). Tyrosine hydroxylase and GFAP immunohistochemistry assays were carried out at 7 days. In addition, animals were evaluated in open field, adhesive removal, staircase and traverse beam tests. Glutathione depletion induced compensatory response in catalase activity and glial response in the in SNpc and no oxidative damage was observed. However, a loss in dopaminergic cells was found. At the same time, animals with glutathione depletion have shown poor performance in behavioral tests except for staircase test. These results suggest that glutathione depletion can be related to sensory-motor dysfunction.
Asunto(s)
Butionina Sulfoximina/toxicidad , Glutatión/metabolismo , Porción Compacta de la Sustancia Negra/metabolismo , Desempeño Psicomotor/efectos de los fármacos , Animales , Cuerpo Estriado/metabolismo , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Locomoción/efectos de los fármacos , Masculino , Microinyecciones , Actividad Motora/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
The aim of our study was to investigate two inter-related hypotheses about the role of the subthalamic nucleus. First that the subthalamic nucleus plays a role in adjusting response thresholds and speed-accuracy trade-offs and second that it is involved in reactive and proactive inhibition and conflict resolution. These were addressed by comparing the performance of 10 patients with Parkinson's disease treated with right subthalamotomy and 12 patients with left subthalamotomy, to 14 unoperated patients with Parkinson's disease and 23 age-matched healthy control participants on a conditional stop signal task and applying the drift diffusion model. Unilateral subthalamotomy significantly improved Parkinson's disease motor signs. Patients with right subthalamotomy had significantly faster Go reaction times with their contra-lesional hand than the unoperated patients and did not differ from the control participants, indicating their speed of response initiation was 'normalized'. However, operated patients made significantly more discrimination errors than unoperated patients and controls, suggesting that subthalamotomy influenced speed-accuracy trade-offs. This was confirmed by the drift diffusion model, revealing that while the unoperated patients had significantly lower drift rate and higher response thresholds than the control participants, the response thresholds for the operated groups did not differ from the controls and the patients with right subthalamotomy had a significantly higher drift rate than unoperated patients and similar to that of controls. The drift diffusion model further established that unlike the control participants, operated patients failed to show context-dependent strategic modulation of response thresholds. The patients with right subthalamotomy could not engage in late phase, fast inhibition of the response and showed minimal proactive inhibition when tested with the contra-lesional hand. These results provide strong evidence that the subthalamic nucleus is involved in response inhibition, in modulating the rate of information accumulation and the response threshold and influencing the balance between speed and accuracy of performance. Accordingly, the subthalamic nucleus can be considered a key component of the cerebral inhibitory network.
Asunto(s)
Inhibición Psicológica , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/cirugía , Núcleo Subtalámico/fisiología , Núcleo Subtalámico/cirugía , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Femenino , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Actividad Motora/fisiología , Pruebas Neuropsicológicas , Enfermedad de Parkinson/fisiopatología , Tiempo de Reacción/fisiología , Detección de Señal Psicológica , Resultado del TratamientoRESUMEN
INTRODUCTION: Zolpidem is a non-benzodiazepine drug used for the therapy of insomnia, which has selectivity for stimulating the effect of GABA-A receptors. Recently, a paradoxical arousing effect of zolpidem in patients with severe brain damage has been repeatedly reported. METHODS: A placebo-controlled magnetic resonance study was conducted to evaluate its effect on BOLD and metabolites spectral signals in a patient with severe brain injuries and an age-matched healthy volunteer. A multi-modal analysis was used to assess aspects in the pharmacologically-induced changes in the resting-state brain metabolism. RESULTS: A significantly increased BOLD signal was transiently localized in the left frontal cortices, bilateral anterior cingulated areas, left thalamus and right head of the caudate nucleus. The healthy subject showed a deactivation of the frontal, parietal and temporal cortices. BOLD signal changes were found to significantly correlate with concentrations of extravascular metabolites in the left frontal cortex. It is discussed that, when zolpidem attaches to modified GABA receptors of neurodormant brain cells, brain activation is induced. This might explain the significant correlations of BOLD signal changes and proton-MRS metabolites in this patient after zolpidem. CONCLUSION: It was concluded that proton-MRS and BOLD signal assessment could be used to study zolpidem-induced metabolic modulation in a resting state.
Asunto(s)
Agonistas de Receptores de GABA-A/uso terapéutico , Oxígeno/sangre , Estado Vegetativo Persistente/sangre , Estado Vegetativo Persistente/fisiopatología , Piridinas/uso terapéutico , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/fisiopatología , Vigilia/efectos de los fármacos , Adulto , Femenino , Agonistas de Receptores de GABA-A/farmacocinética , Hemodinámica , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Estado Vegetativo Persistente/tratamiento farmacológico , Piridinas/farmacocinética , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Resultado del Tratamiento , ZolpidemRESUMEN
PURPOSE: To investigate a possible role of neurotrophins in the memory improving effect of stimulating the basolateral amygdala. METHODS: The BDNF and NGF levels were measured in the hippocampus of fimbria-fornix lesioned male rats after four days of training in the water maze and stimulation of the basolateral amygdala. RESULTS: The behavioral results confirm that daily post-training stimulation of the amygdala improves the learning abilities of the lesioned animals. BDNF increased in lesioned and trained animals, but stimulating the basolateral amygdala induces a significantly greater increase. NGF showed a slight (but significant) increase in fimbria-fornix lesioned and trained animals, but stimulating the amygdala does not produce a further increase. In separate groups of animals we measured the levels of both neurotrophins in acute experiments, after 2 and 24 hours of stimulating the amygdala. BDNF was significantly increased at both times, while NGF showed again only slight increases (significant at 24 h). CONCLUSIONS: These results suggest that the BDNF response to amygdala stimulation might be of functional importance in the observed learning improvement. The changes in NGF are most likely due to the accumulation of this protein after removal of the septal axons.
Asunto(s)
Amígdala del Cerebelo/fisiología , Lesiones Encefálicas/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Fórnix/lesiones , Hipocampo/metabolismo , Memoria/fisiología , Factor de Crecimiento Nervioso/metabolismo , Animales , Lesiones Encefálicas/fisiopatología , Fórnix/fisiopatología , Masculino , Aprendizaje por Laberinto/fisiología , Ratas , Ratas WistarRESUMEN
Recent imaging studies in healthy controls with a conditional stop signal reaction time (RT) task have implicated the subthalamic nucleus (STN) in response inhibition and the pre-supplementary motor area (pre-SMA) in conflict resolution. Parkinson's disease (PD) is characterized by striatal dopamine deficiency and overactivity of the STN and underactivation of the pre-SMA during movement. We used the conditional stop signal RT task to investigate whether PD produced similar or dissociable effects on response initiation, response inhibition and response initiation under conflict. In addition, we also examined inhibition of prepotent responses on three cognitive tasks: the Stroop, random number generation and Hayling sentence completion. PD patients were impaired on the conditional stop signal reaction time task, with response initiation both in situations with or without conflict and response inhibition all being significantly delayed, and had significantly greater difficulty in suppressing prepotent or habitual responses on the Stroop, Hayling and random number generation tasks relative to controls. These results demonstrate the existence of a generalized inhibitory deficit in PD, which suggest that PD is a disorder of inhibition as well as activation and that in situations of conflict, executive control over responses is compromised.
Asunto(s)
Cognición/fisiología , Conflicto Psicológico , Inhibición Psicológica , Enfermedad de Parkinson/fisiopatología , Desempeño Psicomotor/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Enfermedad de Parkinson/psicología , Tiempo de Reacción/fisiología , Test de Stroop , Núcleo Subtalámico/fisiopatologíaRESUMEN
Since the advent of deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD), subsequent cognitive and neuropsychiatric effects of this procedure have become well-chronicled. Yet, thermolitic lesion of the subthalamic nucleus (STN) is still a valid option when DBS cannot be applied, and little has been published regarding its impact on cognition and mood. We examined the cognitive and neuropsychiatric functions of 10 consecutive patients with advanced PD undergoing simultaneous bilateral subthalamotomies. With 24 months of follow-up, the patients, three of whom were on anticholinergics prior to surgery, showed no deterioration in cognitive assessments including verbal fluency. Hypoactive behaviors (depression and apathy) showed lasting improvement, while hyperactive behaviors (euphoria and disinhibition) transiently increased after surgery. Improvement in hypoactive behaviors correlated with improvement in hypokinetic movements, and enhanced hyperactive behaviors followed the course of post-operative hyperkinetic movements. Such correlations may support the role of the STN in modulating limbic connections between the basal ganglia and frontal cortex. The results of this proof-of-concept pilot study suggest the need for larger, long-term, randomized controlled studies to assess motor, neuropsychiatric, behavioral and radiologic correlations after subthalamotomies.
Asunto(s)
Trastornos del Conocimiento/etiología , Trastornos Mentales/etiología , Procedimientos Neuroquirúrgicos/efectos adversos , Enfermedad de Parkinson/cirugía , Núcleo Subtalámico/cirugía , Humanos , Pruebas Neuropsicológicas , Enfermedad de Parkinson/psicologíaRESUMEN
Dopamine is an essential neurotransmitter for many brain functions, and its dysfunction has been implicated in both neurological and psychiatric disorders. Parkinson's disease is an archetypal disorder of dopamine dysfunction characterised by motor, cognitive, behavioural, and autonomic symptoms. While effective for motor symptoms, dopamine replacement therapy is associated not only with motor side-effects, such as levodopa-induced dyskinesia, but also behavioural side-effects such as impulse control disorders (eg, pathological gambling and shopping, binge eating, and hypersexuality), punding (ie, abnormal repetitive non-goal oriented behaviours), and compulsive medication use. We review clinical features, overlapping molecular mechanisms, and a specific cognitive mechanism of habit learning that might underlie these behaviours. We integrate these mechanisms with the emerging view of the basal ganglia as a distributive system involved in the selection and facilitation of movements, acts, and emotions.
Asunto(s)
Antiparkinsonianos/efectos adversos , Trastornos Disruptivos, del Control de Impulso y de la Conducta/inducido químicamente , Dopaminérgicos/efectos adversos , Dopamina/fisiología , Discinesia Inducida por Medicamentos/fisiopatología , Levodopa/efectos adversos , Enfermedad de Parkinson/complicaciones , Antiparkinsonianos/uso terapéutico , Automatismo/fisiopatología , Conducta Compulsiva/inducido químicamente , Conducta Compulsiva/psicología , Trastornos Disruptivos, del Control de Impulso y de la Conducta/fisiopatología , Dopaminérgicos/uso terapéutico , Juego de Azar/psicología , Humanos , Levodopa/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/psicología , Psicosis Inducidas por Sustancias/psicología , Conducta SexualRESUMEN
BACKGROUND: The dopamine precursor 3,4-dihydroxyphenyl-L-alanine (L-DOPA) is currently the most efficacious noninvasive therapy for Parkinson's disease. A major complication of this therapy, however, is the appearance of the abnormal involuntary movements known as dyskinesias. We have developed a model of L-DOPA-induced dyskinesias in mice that reproduces the main clinical features of dyskinesia in humans. METHODS: Dyskinetic symptoms were triggered by repetitive administration of a constant dose of L-DOPA (25 mg/kg, twice a day, for 25 days) in unilaterally 6-hydroxydopamine (6-OHDA) lesioned mice. Mice were examined for behavior, expression of FosB, neuropeptides, and externally regulated kinase (ERK) phosphorylation. RESULTS: Dyskinetic symptoms appear toward the end of the first week of treatment and are associated with L-DOPA-induced changes in DeltaFosB and prodynorphin expression. L-DOPA also induces activation of ERK1/2 in the dopamine-depleted striatum. Interestingly, elevated FosB/DeltaFosB expression occurs exclusively within completely lesioned regions of the striatum, displaying an inverse correlation with remaining dopaminergic terminals. Following acute L-DOPA treatment, FosB expression occurs in direct striatal output neurons, whereas chronic L-DOPA also induces FosB expression in nitric oxide synthase-positive striatal interneurons. CONCLUSIONS: This model provides a system in which genetic manipulation of individual genes can be used to elucidate the molecular mechanisms responsible for the development and expression of dyskinesia.
Asunto(s)
Antiparkinsonianos/efectos adversos , Discinesia Inducida por Medicamentos/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Expresión Génica/efectos de los fármacos , Levodopa/efectos adversos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Animales , Conducta Animal , Western Blotting/métodos , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Modelos Animales de Enfermedad , Dopamina/metabolismo , Esquema de Medicación , Discinesia Inducida por Medicamentos/etiología , Discinesias/etiología , Discinesias/fisiopatología , Encefalinas/genética , Encefalinas/metabolismo , Inmunohistoquímica/métodos , Hibridación in Situ/métodos , Locomoción/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Actividad Motora/efectos de los fármacos , Oxidopamina , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/tratamiento farmacológico , Fosforilación/efectos de los fármacos , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo , ARN Mensajero/metabolismo , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
Bone marrow stromal cells (BMSC) have attracted interest through their possible use for cell therapy in neurological diseases. Recent reports demonstrated that these cells are able to migrate and have potential for neuronal differentiation after transplantation into brain parenchyma. The objective of this work was determine whether rat BMSC express NGF and GDNF, in order to study its potential application for treatment of neurodegenerative diseases. BMSC were harvested from male rats and cultured in DMEM supplemented with 20% fetal bovine serum. At passage 6 the total RNA was isolated using TriZol reactive. RT-PCRs to evaluate the expression of NGF and GDNF using specific primers were carried out. Our results indicate that rat BMSC have potential to produce NGF and GDNF. We have not found any report in favor of GDNF or NGF production from rat BMSC.
Asunto(s)
Células de la Médula Ósea/metabolismo , Factor de Crecimiento Nervioso/biosíntesis , Factores de Crecimiento Nervioso/biosíntesis , Células del Estroma/metabolismo , Animales , Células Cultivadas , Factor Neurotrófico Derivado de la Línea Celular Glial , Guanidinas/farmacología , Masculino , Fenoles/farmacología , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Soluciones/farmacología , Temperatura , Factores de TiempoRESUMEN
Neural stem cells giving rise to neurons and glia cells have been isolated from the embryonic and adult central nervous system. The extent to which they are able to differentiate into cells of non-neural lineages, such as the hematopoietic lineage, is nonetheless unclear. We previously reported the isolation of stem cells from the mouse olfactory bulb neuroepithelium. In the present study, we analysed whether olfactory bulb stem cells (OBSC) can generate cells with hematopoietic features. Cells were prepared from the olfactory bulbs of transgenic mice expressing enhanced green fluorescent protein (EGFP). In culture, transgenic cells proliferated with the same kinetics as wild-type cells. Following mitogen removal, both cell types gave rise to similar numbers of neurons, astrocytes and oligodendrocytes, indicating that EGFP overexpression does not alter OBSC proliferation and differentiation patterns. When these cells were injected into the tail vein of irradiated mice, no hematopoietic cells derived from the OBSC could be recovered in their peripheral blood, spleen or bone marrow. By contrast, when OBSC were transplanted into the adult brain, EGFP-positive cells were found in the striatum and corpus callosum; differentiated cells expressed antigenic markers of neurons and astrocytes. These results suggest that embryonic olfactory bulb stem cells are not endowed with the potential to produce hematopoiesis.
Asunto(s)
Hematopoyesis/fisiología , Proteínas del Tejido Nervioso , Neuronas/fisiología , Bulbo Olfatorio/citología , Células Madre/fisiología , Animales , Astrocitos/metabolismo , Astrocitos/trasplante , Bromodesoxiuridina/metabolismo , Recuento de Células , Diferenciación Celular , Células Cultivadas , Cuerpo Estriado/metabolismo , Cuerpo Estriado/efectos de la radiación , Cuerpo Estriado/trasplante , Citometría de Flujo , Rayos gamma/efectos adversos , Proteína Ácida Fibrilar de la Glía/metabolismo , Proteínas Fluorescentes Verdes , Inmunohistoquímica/métodos , Proteínas de Filamentos Intermediarios/metabolismo , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Nestina , Neuronas/trasplante , Bulbo Olfatorio/embriología , Bulbo Olfatorio/trasplante , Oligodendroglía/metabolismo , Oligodendroglía/trasplante , Trasplante de Células Madre/métodos , Factores de Tiempo , Tubulina (Proteína)/metabolismoRESUMEN
Stimulation of dopamine (DA) receptors in the striatum is essential for voluntary motor activity and for the generation of plasticity at corticostriatal synapses. In the present study, mice lacking DA D1 receptors have been used to investigate the involvement of the D1-like class (D1 and D5) of DA receptors in locomotion and corticostriatal long-term depression (LTD) and long-term potentiation (LTP). Our results suggest that D1 and D5 receptors exert distinct actions on both activity-dependent synaptic plasticity and spontaneous motor activity. Accordingly, the ablation of D1 receptors disrupted corticostriatal LTP, whereas pharmacological blockade of D5 receptors prevented LTD. On the other side, genetic ablation of D1 receptors increased locomotor activity, whereas the D1/D5 receptor antagonist SCH 23390 decreased motor activity in both control mice and mice lacking D1 receptors. Endogenous DA stimulated D1 and D5 receptors in distinct subtypes of striatal neurons to induce, respectively, LTP and LTD. In control mice, in fact, LTP was blocked by inhibiting the D1-protein kinase A pathway in the recorded spiny neuron, whereas the striatal nitric oxide-producing interneuron was presumably the neuronal subtype stimulated by D5 receptors during the induction phase of LTD. Understanding the role of DA receptors in striatal function is essential to gain insights into the neural bases of critical brain functions and of dramatic pathological conditions such as Parkinson's disease, schizophrenia, and drug addiction.
Asunto(s)
Cuerpo Estriado/fisiología , Plasticidad Neuronal/fisiología , Receptores de Dopamina D1/fisiología , Sinapsis/fisiología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Animales , Corteza Cerebral/citología , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/fisiología , Cuerpo Estriado/citología , Cuerpo Estriado/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , GMP Cíclico/metabolismo , Antagonistas de Dopamina/farmacología , Inhibidores Enzimáticos/farmacología , Técnicas In Vitro , Interneuronas/fisiología , Potenciación a Largo Plazo/efectos de los fármacos , Potenciación a Largo Plazo/fisiología , Depresión Sináptica a Largo Plazo/efectos de los fármacos , Depresión Sináptica a Largo Plazo/fisiología , Masculino , Ratones , Ratones Noqueados , Actividad Motora/efectos de los fármacos , Actividad Motora/genética , Neuronas/metabolismo , Neuronas/fisiología , Óxido Nítrico/metabolismo , Técnicas de Placa-Clamp , Receptores de Dopamina D1/antagonistas & inhibidores , Receptores de Dopamina D1/deficiencia , Receptores de Dopamina D5RESUMEN
Introducción. El desarrollo tecnológico contemporáneo y una mejor comprensión de funcionamiento de los ganglios basales obtenidos en las dos últimas décadas, unido a la necesidad de buscar alternativas terapéuticas para los estadíos avanzados y complicados de la enfermedad de parkinson, han condicionado un resurgimiento de la cirugía funcional de los ganglios basales como opción terapéutica. Método. 103 pacientes con enfermedad de Parkinson avanzada fueron evaluados con la escala UPDRS y se sometieron a lesión de la porción interna del globus pallidus. Durante la cirugía, todos los pacientes fueron sometidos a técnicas de semimicrorregistro con el fin de localizar y definir el área sensorimotora del globus pallidus, utilizando un recurso tecnológico propio. Resultados. Más del 93
de los pacientes se benefició con la cirugía, con promedios de mejoría del 40
para la condición motora. En el 95
de los pacientes se abolió la disquinesia y la morbimortalidad fue menor del 10
. Se concluye que la palidotomía posteroventral selectiva es un tratamiento exitoso y relativamente seguro para el tratamiento de las complicaciones motoras evolutivas de la enfermedad de Parkinson avanzada(AU)ç
Asunto(s)
Enfermedad de Parkinson/cirugía , Globo Pálido/cirugíaRESUMEN
Immunological response was characterized in 15 patients with Parkinso's disease intracerebrally transplanted: seven in unilateral and eight in bilateral hemisphere with fetal mesencephalic cells by stereotactical technique. The phenotypic distribution of mononuclear cells in CSF and PB was investigated using monoclonal antibodies. The total protein, albumin and IgG in CSF and albumin, IgA, IgM and IgG Concentration in serum were also analyzed, before and after evolution. A general decrease in CD2+ cells was found in patients with unilateral neurotransplantation during the first semester following trasplant. A small increase in the proportion of CSF CD8+ cells was observed in the first month and in the fourth month in PB. In patients with bilateral intracerebral allografts a decrease in CD2+ and CD4+ cells was found during the first and fourth month. The intrathecal synthesis of IgG during the fourth month was observed in both patients. Results are discussed taking into account the immunosupressor treatment(AU)