RESUMEN
BACKGROUND: Reelin is under epigenetic control and has been reported to be decreased in cortical regions in schizophrenia. METHODS: To establish if expression of reelin is altered in specific cortical, hippocampal or thalamic regions of schizophrenia patients, we measured gene expression of reelin in a postmortem study of elderly patients with schizophrenia and non-affected controls in both hemispheres differentiating between gray and white matter. We compared cerebral postmortem samples (dorsolateral prefrontal cortex BA9 and BA46, superior temporal cortex BA22, entorhinal cortex BA28, sensoric cortex BA1-3, hippocampus, CA4, mediodorsal nucleus of the thalamus) from 12 schizophrenia patients with 13 normal subjects investigating gene expression of reelin in the gray and white matter of both hemispheres by in situ-hybridization. RESULTS: The left prefrontal area (BA9) of schizophrenia patients revealed a decreased expression of reelin-mRNA of 29.1% in the white (p = 0.022) and 13.6% in the gray matter (p = 0.007) compared to the control group. None of the other regions examined showed any statistically significant differences. CONCLUSION: Since reelin is responsible for migration and synapse formation, the decreased gene expression of reelin in the left prefrontal area of schizophrenia patients points to neurodevelopmental deficits in neuronal migration and synaptic plasticity. However, our study group was small, and results should be verified using larger samples.
Asunto(s)
Moléculas de Adhesión Celular Neuronal/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Corteza Prefrontal/metabolismo , ARN Mensajero/análisis , Esquizofrenia/metabolismo , Serina Endopeptidasas/metabolismo , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Moléculas de Adhesión Celular Neuronal/genética , Movimiento Celular/genética , Movimiento Celular/fisiología , Corteza Cerebral/metabolismo , Proteínas de la Matriz Extracelular/genética , Femenino , Expresión Génica , Perfilación de la Expresión Génica , Hipocampo/metabolismo , Humanos , Hibridación in Situ , Masculino , Núcleo Talámico Mediodorsal/metabolismo , Persona de Mediana Edad , Proteínas del Tejido Nervioso/genética , Plasticidad Neuronal , Neuronas/metabolismo , Proteína Reelina , Esquizofrenia/genética , Serina Endopeptidasas/genética , Sinapsis/genética , Sinapsis/metabolismo , Tálamo/metabolismoRESUMEN
Chronic idiopathic singultus (hiccup) is a debilitating condition affecting mostly elderly males. While in the past, pharmacologic singultus treatment was mostly "trial and error," more recently, treatment has become both more evidence based and pathophysiology guided. A combination of an acidity-reducing drug (H(2)-receptor blocker or proton pump inhibitor) with baclofen (gamma-amino-butyric-acid receptor type B agonist) has become the most widely used regimen. Some clinicians replace or supplement baclofen with gabapentin. We present three cases of chronic idiopathic hiccup managed with gabapentin or another alpha-2-delta ligand, pregabalin. This is the first reported use of pregabalin for this indication.
Asunto(s)
Aminas/uso terapéutico , Anticonvulsivantes/uso terapéutico , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Hipo/tratamiento farmacológico , Ácido gamma-Aminobutírico/análogos & derivados , Anciano , Aminas/farmacología , Anticonvulsivantes/farmacología , Canales de Calcio/efectos de los fármacos , Enfermedad Crónica , Ácidos Ciclohexanocarboxílicos/farmacología , Gabapentina , Humanos , Ligandos , Masculino , Persona de Mediana Edad , Pregabalina , Ácido gamma-Aminobutírico/farmacología , Ácido gamma-Aminobutírico/uso terapéuticoRESUMEN
BACKGROUND: Membrane lipids are important mediators of neuronal function. In a postmortem study, we measured membrane lipid components in the left thalamus of schizophrenic patients. This region might play an important role in the pathophysiology of schizophrenia and has not been studied thus far with respect to its membrane lipid composition. METHODS: The study included 18 chronic schizophrenic patients and 23 healthy control subjects. Using lipid extraction and thin-layer chromatography, we measured membrane phospholipids, galactocerebrosides 1 and 2, and sulfatides in thalamus homogenate. RESULTS: The main membrane phospholipid phosphatidylcholine and the major myelin membrane components sphingomyelin and galactocerebrosides 1 and 2 were found to be decreased in schizophrenic patients. In contrast, phosphatidylserine was increased. These lipid contents did not correlate with postmortem intervals and medication doses. There was no difference in the membrane phospholipids lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylglycerol or in sulfatides. CONCLUSIONS: Our results confirm findings of magnetic resonance imaging, postmortem, and gene expression studies. They support the notion of an increased phospholipid breakdown in schizophrenia as a sign for decreased myelination and oligodendrocyte dysfunction.