RESUMEN
The diagnosis of chronic fatigue syndrome (CFS) is mainly symptom-based, and the etiology is still unclear. Here, we evaluated the pathological changes in the brain of a mouse model of CFS and studied the effects of Kampo medicine. A mouse model of CFS was established through six repeated injections of Brucella abortus (BA) every two weeks for a period of 12 weeks. Neuroinflammation was measured by estimating interleukin (IL)-1ß, IL-6, and interferon-gamma (IFN-γ), and oxidative stress by nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) 6 weeks after the last injection. Hippocampal neurogenesis was evaluated through Ki-67, doublecortin (DCX), and 5-bromodeoxyuridine (BrdU) assays. The effects of Kampo medicines (Hochuekkito (TJ-41) and Hachimijiogan (TJ-7)) on neuroinflammation during CFS were studied. The wheel-running activity of mice was decreased by about 50% compared to baseline at 6 weeks after the last BA injection. The levels of IL-1ß, IL-6, 3-NT, and 4-HNE were increased in both the cortex and the hippocampus of CFS mice at 6 weeks after the last BA injection. Hippocampal neurogenesis was unchanged in CFS mice. Treatment with TJ-41 and TJ-7 reduced the expressions of IL-1ß, IL-6, and IFN-γ in the hippocampus but not in the cortex. The results of the present study indicate that neuroinflammation and oxidative stress play important roles in the pathogenesis of CFS. The data further suggest that treatment with TJ-41 and TJ-7 could help reduce the inflammation associated with CFS in the hippocampus, but failed to improve the symptoms in CFS mice.
Asunto(s)
Antiinflamatorios/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Síndrome de Fatiga Crónica/tratamiento farmacológico , Medicina Kampo , Animales , Encéfalo/efectos de los fármacos , Encéfalo/fisiología , Citocinas/inmunología , Modelos Animales de Enfermedad , Proteína Doblecortina , Síndrome de Fatiga Crónica/inmunología , Femenino , Ratones Endogámicos BALB C , Neurogénesis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacosRESUMEN
Sleep can integrate information into existing memory networks, look for common patterns and distil overarching rules, or simply stabilize and strengthen the memory exactly as it was learned. Recent research has shown that sleep facilitates abstraction of gist information as well as integration across multiple memories, insight into hidden solutions, and even the ability to make creative connections between distantly related ideas and concepts. To investigate the effect of sleep on memory organization, 35 normal volunteers were randomly assigned either to the sleep (n = 17) or wake group (n = 18). The sleep subjects performed the Japanese Verbal Learning Test (JVLT), a measure of learning and memory, three times in the evening, and slept. On the following morning (9 h later), they were asked to recall the words on the list. The wake subjects took the same test in the morning, and were asked to recall the words in the same time interval as in the sleep group. The semantic clustering ratio (SCR), divided by the total number of words recalled, was used as an index of memory organization. Our main interest was whether the sleep subjects elicit a greater increase in this measure from the third to the fourth assessments. Time × Group interaction effect on SCR was not significant between the sleep group and wake group as a whole. Meanwhile, the change in the SCR between the third and fourth trials was negatively correlated with duration of nocturnal waking in the sleep group, but not other sleep indices. Based on this observation, further analysis was conducted for subjects in the sleep group who awoke nocturnally for <60 min for comparison with the wake group. A significant Time × Group interaction was noted; these "good-sleepers" showed a significantly greater improvement in the memory index compared with the wake subjects. These results provide the first suggestion that sleep may enhance memory organization, which requires further study.
RESUMEN
Alterations of sleep structure with aging are attributed to change of circadian sleep-wake system and decrease of daytime activity with aging. Prevalence of insomnia and use of sleeping pills increases with age. Physical and psychiatric conditions play important roles in poor sleep in old age, and restless legs syndrome and sleep disordered breathing increase with aging as well. Early and appropriate intervention to insomnia will contribute to improvement of health and quality of life in the elderly.
Asunto(s)
Trastornos del Inicio y del Mantenimiento del Sueño , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Humanos , Lactante , Recién Nacido , Trastornos del Inicio y del Mantenimiento del Sueño/etiologíaRESUMEN
Neurofibrillary tangles (NFT) in Alzheimer's disease (AD) are composed of abnormally phosphorylated tau proteins. Many phosphorylation sites have been reported in the AD brain, and NFT distribution was now roughly classified into 3 stages by Braak stage; this classification is based on pathological studies using the specific silver impregnation technique. The aim of our study was to examine the regional distribution of differently phosphorylated tau proteins with 5 site-specific monoclonal antibodies against the tau proteins, AT8, AT180, HT7, Tau2 and Tau5. We then compared our findings with those obtained from silver-stained NFT in an attempt to clarify the relationship between abnormal phosphorylation sites of the tau protein and NFT development. AT180 and AT8 labeled the highest and Tau2 the lowest density of NFT in any regions, while Tau5 and HT7 showed inconsistent distribution. In the limbic cortex, cornu ammonis, entorhinal cortex and cingulate cortex, silver-stained NFT density significantly correlated with density of NFT labeled with the 5 anti-tau antibodies, but cerebral isocortices showed heterogenous patterns of tau-positive NFT. Quantification of tau-positive regional NFT density showed that the AD-associated phosphorylation process progresses from the C-terminal to the N-terminal of the amino acid sequence, and correlation of Gallyas-stained NFT density with tau-labeled NFT density was more significant in the limbic cortices than the cerebral isocortices, which implies that stereotypical phosphorylation occurs in the limbic structures.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Química Encefálica/fisiología , Proteínas tau/análisis , Enfermedad de Alzheimer/patología , Anticuerpos Monoclonales , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Ovillos Neurofibrilares/metabolismo , Ovillos Neurofibrilares/patología , Neuronas/química , Fosforilación , Tinción con Nitrato de PlataAsunto(s)
Ingestión de Líquidos , Disomnias/etiología , Ingestión de Alimentos , Adulto , Preescolar , Humanos , LactanteRESUMEN
Machado-Joseph disease (MJD) is a dominantly inherited spinocerebellar disorder, and expansions of trinucleotide (CAG) at chromosome 14 have been shown to be the locus of this disorder. Polyglutamine CAG stretches in the neuronal cytoplasms and nuclei were studied with immunolabeling using 1C2, a monoclonal antibody recognizing polyglutamine stretches, and polyclonal antiubiquitin antibody in six genetically verified cases of MJD. 1C2 clearly labeled two types of neuronal intranuclear inclusions (NII) and neuronal cytoplasmic inclusions (NCI) in the substantia nigra, pontine nucleus, dentate nucleus and spinal anterior horn where NII and NCI were also positive for ubiquitin, as were extracellular dot-like structures and oligodendroglial inclusions. 1C2-positive NII and NCI had a lesion-specific distribution. While the spinal motoneurons contained only 1C2-positive NCI and lacked 1C2-positive NII, the ventral pontine nucleus neurons had many 1C2-positive NII and few 1C2-positive NCI. Semi-quantitative examination of NII and NCI positive for 1C2 or ubiquitin demonstrated that there were more 1C2-positive NII and NCI than ubiquitin-positive ones. It is noteworthy that the nuclei of the spinal motoneurons lacked 1C2-positive immunoreactivity, so that ubiquitination of 1C2-positive structures is presumed to occur late in the course of the disease.