RESUMO
Proliferation and differentiation of retinal progenitor cells (RPCs) are tightly controlled by extrinsic cues and distinct combinations of transcription factors leading to the generation of retinal cell type diversity. In this context, we investigated the role of the protein tyrosine phosphatase interacting protein 51 (PTPIP51) in the differentiation of RPCs. The expression pattern of PTPIP51 was analyzed by immunostaining during post-natal retinal development in the rat. Ex vivo electroporation has been used to silence or misexpress PTPIP51 in post-natal retinal explants, and the retinal phenotype was investigated after 3-7days in vitro (div). PTPIP51 expression in the retina started postnatally and was maintained throughout adulthood, especially in retinal ganglion cells and in the inner segment of photoreceptor cells. Silencing of Ptpip51 expression in postnatal retina failed to modify the commitment of late RPCs in the different lineages but severely impaired the final differentiation of photoreceptors, observed by a decrease in the fraction of Rhodopsin-positive cells after 7div. By contrast, misexpression of PTPIP51 in early or late RPCs failed to modify the differentiation of the RPCs. Our data demonstrate that PTPIP51 is implicated in the differentiation process of immature photoreceptors. Because PTPIP51 is specifically localized in the inner segment, PTPIP51 may contribute to the complex stage of maturation of the apical segment of these cells.
Assuntos
Células-Tronco Neurais/fisiologia , Neurogênese/fisiologia , Células Fotorreceptoras de Vertebrados/fisiologia , Proteínas Tirosina Fosfatases/metabolismo , Retina/crescimento & desenvolvimento , Retina/fisiologia , Animais , Western Blotting , Eletroporação , Imunofluorescência , Inativação Gênica , Hibridização In Situ , Proteínas Tirosina Fosfatases/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Técnicas de Cultura de TecidosAssuntos
Encéfalo/metabolismo , Vias Neurais/metabolismo , Neurônios/metabolismo , Neurotransmissores/deficiência , Doença de Parkinson/metabolismo , Animais , Encéfalo/patologia , Encéfalo/fisiopatologia , Regulação para Baixo/fisiologia , Resistência a Medicamentos/fisiologia , Humanos , Vias Neurais/patologia , Vias Neurais/fisiopatologia , Neurônios/patologia , Neurônios/ultraestrutura , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Receptores Dopaminérgicos/metabolismo , Receptores Dopaminérgicos/ultraestrutura , Regulação para Cima/fisiologiaRESUMO
In the past, functional changes in the circuitry of the basal ganglia that occur in Parkinson's disease were primarily analyzed with electrophysiological and 2-deoxyglucose measurements. The increased activity of the subthalamic nucleus (STN) observed has been attributed to a reduction in inhibition mediated by the external segment of the globus pallidus (GPe), secondary to the loss of dopaminergic-neuron influence on D2-receptor-bearing striato-pallidal neurons. More recently, in situ hybridization studies of cytochrome oxidase subunit I have confirmed the overactivity of the STN in the parkinsonian state. In addition, this technique has provided evidence that the change in STN activity is owing not only to decreased inhibition from the GPe but to hyperactivity of excitatory inputs from the parafascicular nucleus of the thalamus and the pedunculopontine nucleus in the brainstem.
Assuntos
Gânglios da Base/metabolismo , Dopamina/metabolismo , Globo Pálido/metabolismo , Doença de Parkinson/metabolismo , Núcleo Subtalâmico/metabolismo , Gânglios da Base/enzimologia , Encéfalo/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Globo Pálido/enzimologia , Humanos , Hibridização In Situ , Modelos Neurológicos , Inibição Neural , Vias Neurais , Doença de Parkinson/fisiopatologia , Núcleo Subtalâmico/enzimologiaRESUMO
Using a combination of metabolic measurement and retrograde tracing, we show that the neurons in the pedunculopontine nucleus and parafascicular nucleus of the thalamus that project to the subthalamic nucleus are hyperactive after nigrostriatal dopaminergic denervation in rats. In Parkinson's disease, the loss of dopaminergic neurons induces a cascade of functional changes in the basal ganglia circuitry including a hyperactivity of the subthalamic nucleus. This hyperactivity is thought to be due to a diminution of the inhibitory pallidal influence. However, recent studies have suggested that other cerebral structures are involved in the subthalamic neuronal hyperactivity. This study was undertaken to identify these cerebral structures. Neurons projecting to the subthalamic nucleus were identified by retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase, injected into the subthalamic nucleus of rats with 6-hydroxydopamine unilateral lesion of the substantia nigra pars compacta and sham-lesioned animals. Metabolic activity was determined in the same neurons using in situ hybridization for the first subunit of cytochrome oxidase messenger RNA, a metabolic marker, and image analysis. Horseradish peroxidase-labeled neurons were found in the globus pallidus, parafascicular and pedunculopontine nucleus and sometimes in raphe nuclei and the substantia nigra pars compacta. Measurement of metabolic activity was performed for the globus pallidus, the pedunculopontine and parafascicular nuclei. The expression level of the first subunit of cytochrome oxidase messenger RNA in neurons projecting to the subthalamic nucleus was 62% higher in parafascicular neurons and 123% higher in pedunculopontine neurons in 6-hydroxydopamine-lesioned rats, compared to sham-lesioned animals. An increase was also observed in the globus pallidus, but did not reach significance. Our results suggest that hyperactivity of subthalamic neurons could be due, at least in part, to an increase of excitatory input arising from the pedunculopontine and parafascicular nuclei. These data also suggest that the latter structures may play an important role in the physiopathology of Parkinson's disease.
Assuntos
Metabolismo Energético/fisiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Núcleos Intralaminares do Tálamo/metabolismo , Núcleos Intralaminares do Tálamo/fisiopatologia , Vias Neurais/metabolismo , Vias Neurais/fisiopatologia , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/fisiopatologia , Ponte/metabolismo , Ponte/fisiopatologia , Núcleo Subtalâmico/metabolismo , Núcleo Subtalâmico/fisiopatologia , Animais , Transporte Axonal/efeitos dos fármacos , Transporte Axonal/fisiologia , Modelos Animais de Doenças , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Núcleos Intralaminares do Tálamo/patologia , Masculino , Degeneração Neural/metabolismo , Degeneração Neural/fisiopatologia , Vias Neurais/patologia , Neurônios/metabolismo , Neurônios/patologia , Oxidopamina/farmacologia , Transtornos Parkinsonianos/patologia , Ponte/patologia , Ratos , Ratos Sprague-Dawley , Núcleo Subtalâmico/patologiaRESUMO
A case of Clofazimine enteropathy is reported, diagnosed on the demonstration of red brown birefringent crystals in the small bowel mucosa and submucosa as well as in the mesenteric lymph nodes whereas the clinical and radiological signs appear to be non specific. After the withdrawal of the drug, a clear improvement of the symptoms was achieved only under a gluten free diet. The possibility of such accidents, sometimes lethal, suggests the restriction of clofazimine to leprosy.