RESUMEN
Fused in sarcoma (FUS) is genetically and clinicopathologically linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). We have previously reported that intranuclear interactions of FUS and splicing factor, proline- and glutamine-rich (SFPQ) contribute to neuronal homeostasis. Disruption of the FUS-SFPQ interaction leads to an increase in the ratio of 4-repeat tau (4R-tau)/3-repeat tau (3R-tau), which manifests in FTLD-like phenotypes in mice. Here, we examined FUS-SFPQ interactions in 142 autopsied individuals with FUS-related ALS/FTLD (ALS/FTLD-FUS), TDP-43-related ALS/FTLD (ALS/FTLD-TDP), progressive supranuclear palsy, corticobasal degeneration, Alzheimer's disease, or Pick's disease as well as controls. Immunofluorescent imaging showed impaired intranuclear co-localization of FUS and SFPQ in neurons of ALS/FTLD-FUS, ALS/FTLD-TDP, progressive supranuclear palsy and corticobasal degeneration cases, but not in Alzheimer's disease or Pick's disease cases. Immunoprecipitation analyses of FUS and SFPQ revealed reduced interactions between the two proteins in ALS/FTLD-TDP and progressive supranuclear palsy cases, but not in those with Alzheimer disease. Furthermore, the ratio of 4R/3R-tau was elevated in cases with ALS/FTLD-TDP and progressive supranuclear palsy, but was largely unaffected in cases with Alzheimer disease. We concluded that impaired interactions between intranuclear FUS and SFPQ and the subsequent increase in the ratio of 4R/3R-tau constitute a common pathogenesis pathway in FTLD spectrum diseases.
Asunto(s)
Esclerosis Amiotrófica Lateral/metabolismo , Degeneración Lobar Frontotemporal/metabolismo , Neuronas/metabolismo , Factor de Empalme Asociado a PTB/metabolismo , Proteína FUS de Unión a ARN/metabolismo , Proteinopatías TDP-43/metabolismo , Anciano , Esclerosis Amiotrófica Lateral/patología , Encéfalo/metabolismo , Encéfalo/patología , Femenino , Degeneración Lobar Frontotemporal/patología , Humanos , Masculino , Persona de Mediana Edad , Neuronas/patología , Proteinopatías TDP-43/patología , Proteínas tau/metabolismoRESUMEN
Although dietary behaviors are affected by neuropsychiatric disorders, various environmental conditions can have strong effects as well. We found that mice under multiple stresses, including social isolation, intermittent high-fat diet, and physical restraint, developed feeding behavior patterns characterized by a deviated bait approach (fixated feeding). All the tested stressors affected dopamine release at the nucleus accumbens (NAcc) shell and dopamine normalization reversed the feeding defects. Moreover, inhibition of dopaminergic activity in the ventral tegmental area that projects into the NAcc shell caused similar feeding pattern aberrations. Given that the deviations were not consistently accompanied by changes in the amount consumed or metabolic factors, the alterations in feeding behaviors likely reflect perturbations to a critical stress-associated pathway in the mesolimbic dopamine system. Thus, deviations in feeding behavior patterns that reflect reward system abnormalities can be sensitive biomarkers of psychosocial and physical stress.
RESUMEN
Patients who need home care are often old, of delicate health, and take many different medications. In order to take these medicines properly, not only the patient him/herself but also their family, the helper, and the visiting nurse must have the correct information about them. Since home care is typically carried out by several medical professionals from different fields, we sent out questionnaires to pharmacists and nurse care professionals. From the results, we found that there was a discrepancy in level of interest in medications between the health care professionals who treat the patients daily and pharmacists who hardly visit the patient's home. As for dispensing, from a risk management point of view, standardization of the colors used to sort the medicine which is packed into one medicine package is required. And for pharmacists, the needs for more cooperation with physicians were pointed out.