RESUMEN
False-positive results on combined positron emission tomography/computed tomography can complicate detection and surveillance of head and neck cancers. We present a rare case of false-positive contralateral [18F]-2-fluoro-2-deoxy-D-glucose tongue uptake after hypoglossal nerve paralysis caused by squamous cell carcinoma originating from the base of the tongue.
Asunto(s)
Enfermedades del Nervio Hipogloso/diagnóstico , Enfermedades del Nervio Hipogloso/metabolismo , Imagen Multimodal , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Lengua/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Lengua/diagnóstico por imagenRESUMEN
Hereditary amyloidosis of the Finnish type (HAF, or familial amyloid polyneuropathy type IV) is an autosomal dominant disease that has been described most commonly in the Finnish population but has also been found in some other countries. Herein we report the first German family whose members suffer from this condition. There are no known Finnish ancestors. We performed clinical and electrophysiological examinations in 22 members of this family. All symptomatic family members suffered from facial palsy, and most of them had peripheral neuropathy. One patient had confirmed corneal lattice dystrophy. Additional symptoms were hypoglossal nerve involvement in 5 patients and oculomotor nerve palsy in 1 patient. The lips of all older patients appeared thickened. The causative G654A mutation in the gelsolin gene was found in all affected family members.
Asunto(s)
Neuropatías Amiloides Familiares/fisiopatología , Enfermedades de los Nervios Craneales/fisiopatología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Adolescente , Adulto , Anciano , Neuropatías Amiloides Familiares/diagnóstico , Neuropatías Amiloides Familiares/genética , Distrofias Hereditarias de la Córnea/diagnóstico , Distrofias Hereditarias de la Córnea/metabolismo , Distrofias Hereditarias de la Córnea/fisiopatología , Enfermedades de los Nervios Craneales/diagnóstico , Enfermedades de los Nervios Craneales/genética , Nervios Craneales/metabolismo , Nervios Craneales/fisiopatología , Análisis Mutacional de ADN , Evaluación de la Discapacidad , Electrodiagnóstico , Enfermedades del Nervio Facial/metabolismo , Enfermedades del Nervio Facial/fisiopatología , Femenino , Finlandia , Gelsolina/genética , Marcadores Genéticos/genética , Pruebas Genéticas , Genotipo , Alemania , Humanos , Enfermedades del Nervio Hipogloso/metabolismo , Enfermedades del Nervio Hipogloso/fisiopatología , Patrón de Herencia/genética , Masculino , Persona de Mediana Edad , Mutación/genética , Examen Neurológico , Enfermedades del Nervio Oculomotor/diagnóstico , Enfermedades del Nervio Oculomotor/metabolismo , Enfermedades del Nervio Oculomotor/fisiopatología , Nervios Periféricos/metabolismo , Nervios Periféricos/fisiopatología , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/genética , Adulto JovenRESUMEN
The current work has documented the expression of the mRNAs for serine protease inhibitor 3 (SPI-3) in the facial and hypoglossal nuclei following peripheral nerve transection by using the in situ hybridization method. The signals appeared 6 hour after nerve injury; they became stronger on day 1 of injury and persisted for 21 days. SPI-3 may be involved during early events of modulating the activities of serine proteases following nerve injury. Such activities may include synaptic stripping and re-organization and facilitation of glial cell reaction to nerve injury. In the later stages of nerve injury SPI-3 may enhance neuronal survival, growth of neurites and re-establishment of synaptic contacts in the facial and hypoglossal nuclei. Hypoglossal but not facial nerve transection caused the expression of mRNAs for SPI-3 in the pineal gland. The signals appeared 6 hours after nerve injury and persisted for 21 days. The significance of this observation is not known but it indicates that the pineal gland senses injury to some peripheral nerves including the hypoglossal nerve. The study has also showed that axotomy of the sciatic nerve did not give rise to the up-regulation of the mRNAs for SPI-3 in the spinal cord. There was no hybridization signals in the lumbar segments; an indication that SPI-3 may not form part of molecules that are released during sciatic nerve transaction by the neural and non-neural cells of the spinal cord. At the moment there are no antibodies for SPI-3 and therefore future studies are needed to verify the findings. It will be interesting also to study on the role of pineal gland during peripheral nerve injuries.
Asunto(s)
Proteínas de Fase Aguda/genética , Traumatismos del Nervio Facial/metabolismo , Enfermedades del Nervio Hipogloso/metabolismo , Neuronas Motoras/metabolismo , Sistema Nervioso Periférico/lesiones , ARN Mensajero/metabolismo , Serpinas/genética , Animales , Nervio Facial/metabolismo , Nervio Facial/patología , Traumatismos del Nervio Facial/genética , Traumatismos del Nervio Facial/patología , Conos de Crecimiento/metabolismo , Conos de Crecimiento/ultraestructura , Nervio Hipogloso/metabolismo , Nervio Hipogloso/patología , Enfermedades del Nervio Hipogloso/genética , Enfermedades del Nervio Hipogloso/patología , Hibridación in Situ , Masculino , Neuronas Motoras/patología , Regeneración Nerviosa/genética , Vías Nerviosas/metabolismo , Vías Nerviosas/patología , Nervios Periféricos/inmunología , Nervios Periféricos/patología , Sistema Nervioso Periférico/metabolismo , Sistema Nervioso Periférico/patología , Glándula Pineal/metabolismo , Glándula Pineal/patología , Ratas , Ratas Wistar , Recuperación de la Función , Rombencéfalo/metabolismo , Rombencéfalo/patología , Médula Espinal/metabolismo , Médula Espinal/patología , Sinapsis/metabolismo , Sinapsis/ultraestructuraRESUMEN
Disrupted peripheral nerves are typically sutured as spontaneous recovery does not always occur. However, the molecular mechanisms involved in nerve regeneration following end-to-end nerve suture are obscure. Here, we investigated effects of end-to-end nerve suture after peripheral nerve transection on motor neurons, using the C57BL/6J mouse hypoglossal nerve injury model. In this animal model, 60-80% of injured motor neurons gradually progress to neuronal death, while the remaining injured neurons survive and regenerate. Mice were divided into the Cut and Suture groups. In the Cut group, the right hypoglossal nerve was transected. In the Suture group, the right hypoglossal nerve was transected and then was repaired using end-to-end nerve suture. We assessed differences between the Cut and Suture groups by analyzing the neuronal survival rate by thionine staining and the nerve terminal regeneration rate by vesicular acetylcholine transporter (VAChT) immunohistochemistry, which is a marker for cholinergic presynaptic terminal. We found that 82.9% of motor neurons survived in the Suture group, whereas only 39.2% of motor neurons did in the Cut group 56 days after surgery. At that time point, 86% of presynaptic terminals compared to controls were regenerated in the Suture group, and 21% were regenerated in the Cut group. These results demonstrate that peripheral nerve suture prevented death of nerve-transected motor neurons and promoted nerve regeneration. We also examined expression profiles of major survival and death signal-associated genes in hypoglossal nuclei using in situ hybridization and real-time polymerase chain reaction (PCR). Although most of the survival- and death-associated genes were regulated in a similar manner in both groups, expression of BH3-only protein Noxa mRNA was significantly lower in the Suture than in the Cut group. A significant suppression of Noxa expression by the Suture may be a major reason why nerve suture induces survival and regeneration of nerve-injured motor neurons.
Asunto(s)
Enfermedades del Nervio Hipogloso/metabolismo , Enfermedades del Nervio Hipogloso/cirugía , Nervio Hipogloso/metabolismo , Nervio Hipogloso/cirugía , Regeneración Nerviosa/fisiología , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis/genética , Biomarcadores/análisis , Biomarcadores/metabolismo , Supervivencia Celular/genética , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/fisiología , Nervio Hipogloso/fisiopatología , Enfermedades del Nervio Hipogloso/fisiopatología , Masculino , Ratones , Ratones Endogámicos C57BL , Proteína Quinasa 3 Activada por Mitógenos/genética , Neuronas Motoras/metabolismo , Degeneración Nerviosa/etiología , Degeneración Nerviosa/genética , Degeneración Nerviosa/metabolismo , Procedimientos Neuroquirúrgicos/normas , Terminales Presinápticos/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Técnicas de Sutura/normas , Suturas/normas , Proteínas de Transporte Vesicular de Acetilcolina/metabolismoRESUMEN
We previously identified melanocortin receptor 4 (MC4R) in a search for genes associated with hypoglossal nerve regeneration. As melanocortins promote nerve regeneration after axonal injury, we investigated whether MC4R functions as a key receptor for peripheral nerve regeneration. In situ hybridization revealed that MC4R mRNA is induced in mouse hypoglossal motor neurons after axonal injury, whereas mRNAs for MC1R, MC2R, MC3R, and MC5R are not expressed either before or after nerve injury. This result was confirmed by RT-PCR. The level of MC4R mRNA expression increased significantly from day 3 after axotomy, reached a peak on day 5, and decreased to the control level on day 14. Similar induction of MC4R was observed in axotomized mouse dorsal root ganglia (DRGs). MC4R mRNA expression was induced exclusively among the MCR family in the L4-6 DRG after sciatic nerve injury. We further examined whether alpha-melanocortin stimulating hormone (alpha-MSH) promotes neurite elongation via MC4R. In mouse DRG neuron culture, alpha-MSH significantly promoted neurite outgrowth at a concentration of 10(-8) mol/L. This neurite-elongation effect was entirely inhibited by the addition of a selective MC4R blocker, JKC-363. Therefore, it is concluded that alpha-MSH could stimulate neurite elongation via MC4R in DRG neurons. The present results suggest that induction of MC4R is crucial for motor and sensory neurons to regenerate after axonal injury.
Asunto(s)
Regulación de la Expresión Génica/fisiología , Enfermedades del Nervio Hipogloso/patología , Neuronas Motoras/metabolismo , Neuronas Aferentes/metabolismo , Receptor de Melanocortina Tipo 4/metabolismo , Animales , Células Cultivadas , Relación Dosis-Respuesta a Droga , Ganglios Espinales/patología , Regulación de la Expresión Génica/efectos de los fármacos , Enfermedades del Nervio Hipogloso/metabolismo , Hibridación in Situ/métodos , Masculino , Hormonas Estimuladoras de los Melanocitos/farmacología , Ratones , Ratones Endogámicos C57BL , Neuronas Motoras/citología , Neuronas Motoras/efectos de los fármacos , Factor de Crecimiento Nervioso/farmacología , Neuritas/efectos de los fármacos , Neuritas/fisiología , Neuronas Aferentes/citología , Neuronas Aferentes/efectos de los fármacos , Péptidos Cíclicos/farmacología , ARN Mensajero/metabolismo , Receptor de Melanocortina Tipo 4/antagonistas & inhibidores , Receptor de Melanocortina Tipo 4/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Factores de Tiempo , beta-MSH/farmacologíaRESUMEN
We examined changes in the expression of Smad family members, which transduce signals from TGF-beta superfamily ligands, following hypoglossal nerve injury. RT-PCR and in situ hybridization revealed that Smad1, 2, 3 and 4 mRNAs were significantly up-regulated in injured side, whereas Smad8 mRNA was down-regulated. Immunohistochemistry and Western blotting analysis confirmed the alterations of Smad1, 2 and 4 in injured neurons. These results suggest that the Smad signaling may be important for nerve regeneration.
Asunto(s)
Enfermedades del Nervio Hipogloso/metabolismo , Traumatismos del Nervio Hipogloso , Nervio Hipogloso/metabolismo , Neuronas Motoras/metabolismo , Regeneración Nerviosa , Proteínas Smad/metabolismo , Animales , Axotomía , Regulación hacia Abajo/genética , Regulación de la Expresión Génica/genética , Nervio Hipogloso/fisiopatología , Enfermedades del Nervio Hipogloso/fisiopatología , Inmunohistoquímica , Masculino , Ratas , Ratas Wistar , Degeneración Retrógrada/genética , Degeneración Retrógrada/metabolismo , Degeneración Retrógrada/fisiopatología , Proteínas Smad/genética , Proteína Smad1/genética , Proteína Smad1/metabolismo , Proteína smad3/genética , Proteína smad3/metabolismo , Proteína Smad4/genética , Proteína Smad4/metabolismo , Proteína Smad8/genética , Proteína Smad8/metabolismo , Regulación hacia Arriba/genéticaRESUMEN
Heparan sulfate proteoglycans, which bear long chains of heparan sulfate glycosaminoglycan, play significant roles during embryogenesis, including the formation of the CNS. However, their involvement in nerve regeneration has not yet been clarified. Here, we found that the mRNA expression of EXT2, one of the crucial enzymes for heparan sulfate-glycosaminoglycan synthesis, was markedly up-regulated in injured hypoglossal motor neurons after axotomy. In addition, immunohistochemical staining with an antibody specific for heparan sulfate-glycosaminoglycan chains demonstrated increased expression of heparan sulfate-glycosaminoglycan chains in the injured nucleus. Furthermore, the mRNA expressions of glypican-1 and syndecan-1, which are both well-known heparan sulfate proteoglycans, were prominently up-regulated in injured motor neurons. These results suggest that the biosynthesis of heparan sulfate chains promoted by EXT2 is activated in injured motor neurons, and that glypican-1 and syndecan-1 are potent candidates for heparan sulfate proteoglycans involved in peripheral nerve regeneration.
Asunto(s)
Regulación de la Expresión Génica/fisiología , Heparitina Sulfato/metabolismo , Enfermedades del Nervio Hipogloso/metabolismo , N-Acetilglucosaminiltransferasas/metabolismo , Factor de Transcripción Activador 3/genética , Factor de Transcripción Activador 3/metabolismo , Animales , Axotomía/métodos , Regulación de la Expresión Génica/efectos de los fármacos , Inmunohistoquímica/métodos , Hibridación in Situ/métodos , Ratones , Ratones Endogámicos C57BL , N-Acetilglucosaminiltransferasas/genética , Polisacárido Liasas/farmacología , ARN Mensajero/metabolismo , Factores de TiempoRESUMEN
To identify proteins implicated in peripheral nerve regeneration, we performed two-dimensional polyacrylamide gel electrophoresis and subsequent mass spectrometry analysis using nerve-injured hypoglossal nuclei of rat. We have identified annexin III (ANX III/ANX A3) as an induced protein after rat hypoglossal nerve injury. ANX III is known as a Ca2+-dependent phospholipid-binding protein, but its physiological function is mostly unknown. By in situ hybridization and immunohistochemistry, we demonstrated that ANX III expression was induced specifically in activated (axotomy-stimulated) microglia after nerve injury. ANX III was the most prominent ANX expressed in microglia of the major ANX family members (ANX I-VI). Hybridization signals for other ANX mRNAs (II, IV, V, and VI) were mainly observed in neuronal cells, and no significant hybridization signal for ANX I mRNA was detected in hypoglossal nuclei. In cultured microglia, ATP treatment induced ANX III translocation to the ruffling membrane where F-actin was accumulated. Further in vitro studies revealed that ANX III was not secreted and had F-actin binding activity in a Ca2+-dependent manner. These results suggest that ANX III may be a Ca2+-dependent mediator between phospholipids and F-actin in microglia stimulated by peripheral nerve injury.
Asunto(s)
Anexina A3/metabolismo , Axones/metabolismo , Microglía/metabolismo , Neuronas Motoras/metabolismo , Regeneración Nerviosa/fisiología , Nervios Periféricos/metabolismo , Actinas/metabolismo , Animales , Animales Recién Nacidos , Anexina A3/genética , Señalización del Calcio/fisiología , Membrana Celular/metabolismo , Movimiento Celular/fisiología , Células Cultivadas , Gliosis/genética , Gliosis/metabolismo , Gliosis/fisiopatología , Nervio Hipogloso/citología , Nervio Hipogloso/metabolismo , Enfermedades del Nervio Hipogloso/metabolismo , Enfermedades del Nervio Hipogloso/fisiopatología , Traumatismos del Nervio Hipogloso , Masculino , Traumatismos de los Nervios Periféricos , Nervios Periféricos/citología , Fosfolípidos/metabolismo , Unión Proteica/fisiología , Transporte de Proteínas/fisiología , ARN Mensajero , Ratas , Ratas Wistar , Regulación hacia Arriba/fisiologíaRESUMEN
A 58-year-old woman, with nonsmall cell carcinoma, had multiple metastasis on 2-F-18 FDG positron emission tomography imaging. The right hemitongue had increased activity as compared with the left. This was not the result of the presence of a metastasis to the tongue, as shown by a negative computed tomography scan of the region and failure to demonstrate a lesion over a period of weeks. Uptake was likely related to right hemiglossal muscle activity. This was made more apparent by decreased uptake on the opposite side of the tongue (up to the midline) as a result of left cranial nerve XII paralysis.
Asunto(s)
Fluorodesoxiglucosa F18 , Enfermedades del Nervio Hipogloso/diagnóstico por imagen , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/inervación , Parálisis/diagnóstico por imagen , Lengua/diagnóstico por imagen , Lengua/inervación , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/secundario , Diagnóstico Diferencial , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Humanos , Enfermedades del Nervio Hipogloso/complicaciones , Enfermedades del Nervio Hipogloso/diagnóstico , Enfermedades del Nervio Hipogloso/metabolismo , Persona de Mediana Edad , Músculo Esquelético/metabolismo , Parálisis/diagnóstico , Parálisis/etiología , Parálisis/metabolismo , Tomografía de Emisión de Positrones/métodos , Radiofármacos/farmacocinética , Lengua/metabolismo , Neoplasias de la Lengua/diagnóstico por imagen , Neoplasias de la Lengua/metabolismo , Neoplasias de la Lengua/secundarioRESUMEN
The survival of neurons is maintained primarily by neurotrophic factors that suppress the apoptotic program. Axotomy or removal of peripheral targets causes neuronal cell death, but the mechanisms involved in the induction of this type of cell death remain poorly understood. Here, we show that DP5/Harakiri, a Bcl-2 homology domain 3-only member of the Bcl-2 family, is induced in motoneurons after transection of the hypoglossal nerve in mice and in sympathetic neurons after nerve growth factor (NGF) withdrawal. To assess the role of DP5 in neuronal cell death, mutant mice deficient in DP5 were generated by gene targeting. DP5-/- mice were viable and exhibited normal postnatal development. Notably, motoneurons from DP5-/- mice were highly protected from cell death induced by resection of the hypoglossal nerve compared with motoneurons from DP5+/+ littermate mice. In addition, deficiency of DP5 in superior cervical ganglia (SCG) neurons resulted in delayed neuronal cell death triggered by NGF withdrawal. Analysis of SCG neurons from DP5-/- mice revealed increased preservation of mitochondrial membrane potential and reduced activation of caspase-3 compared with neurons from wild-type mice. These results indicate that DP5 plays an important role in neuronal cell death induced by axotomy and NGF deprivation through the regulation of mitochondrial function and caspase-3 activation.