Asunto(s)
Antirreumáticos , Enfermedades de la Retina , Antirreumáticos/efectos adversos , Humanos , Hidroxicloroquina/efectos adversos , Enfermedades de la Retina/inducido químicamente , Enfermedades de la Retina/diagnóstico , Enfermedades de la Retina/genética , Tomografía de Coherencia Óptica , Pruebas del Campo VisualRESUMEN
NMDA glutamate receptors (NMDARs) have critical functional roles in the nervous system but NMDAR over-activity can contribute to neuronal damage. The open channel NMDAR blocker, memantine is used to treat certain neurodegenerative diseases, including Parkinson's disease (PD) and is well tolerated clinically. We have investigated memantine block of NMDARs in substantia nigra pars compacta (SNc) dopamine neurones, which show severe pathology in PD. Memantine (10 µM) caused robust inhibition of whole-cell (synaptic and extrasynaptic) NMDARs activated by NMDA at a high concentration or a long duration, low concentration. Less memantine block of NMDAR-EPSCs was seen in response to low frequency synaptic stimulation, while responses to high frequency synaptic stimulation were robustly inhibited by memantine; thus memantine inhibition of NMDAR-EPSCs showed frequency-dependence. By contrast, MK-801 (10 µM) inhibition of NMDAR-EPSCs was not significantly different at low versus high frequencies of synaptic stimulation. Using immunohistochemistry, confocal imaging and stereological analysis, NMDA was found to reduce the density of cells expressing tyrosine hydroxylase, a marker of viable dopamine neurones; memantine prevented the NMDA-evoked decrease. In conclusion, memantine blocked NMDAR populations in different subcellular locations in SNc dopamine neurones but the degree of block depended on the intensity of agonist presentation at the NMDAR. This profile may contribute to the beneficial effects of memantine in PD, as glutamatergic activity is reported to increase, and memantine could preferentially reduce over-activity while leaving some physiological signalling intact.
Asunto(s)
Neuronas Dopaminérgicas/efectos de los fármacos , Memantina/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Sustancia Negra/efectos de los fármacos , Animales , Recuento de Células , Maleato de Dizocilpina/farmacología , Neuronas Dopaminérgicas/metabolismo , Neuronas Dopaminérgicas/fisiología , Relación Dosis-Respuesta a Droga , Agonistas de Aminoácidos Excitadores/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciales Postsinápticos Excitadores/fisiología , Masculino , Memantina/farmacología , N-Metilaspartato/farmacología , Degeneración Nerviosa/prevención & control , Ratas , Receptores de N-Metil-D-Aspartato/fisiología , Sustancia Negra/metabolismo , Sustancia Negra/fisiología , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Social evolution in honey bees has produced strong queen-worker dimorphism for plastic traits that depend on larval nutrition. The honey bee developmental programme includes both larval components that determine plastic growth responses to larval nutrition and nurse components that regulate larval nutrition. We studied how these two components contribute to variation in worker and queen body size and ovary size for two pairs of honey bee lineages that show similar differences in worker body-ovary size allometry but have diverged over different evolutionary timescales. Our results indicate that the lineages have diverged for both nurse and larval developmental components, that rapid changes in worker body-ovary size allometry may disrupt queen development and that queen-worker dimorphism arises mainly from discrete nurse-provided nutritional environments, not from a developmental switch that converts variable nutritional environments into discrete phenotypes. Both larval and nurse components have likely contributed to the evolution of queen-worker dimorphism.
Asunto(s)
Abejas/crecimiento & desarrollo , Evolución Biológica , Tamaño Corporal , Conducta Social , Animales , Conducta Alimentaria , Femenino , Larva/crecimiento & desarrollo , Ovario/crecimiento & desarrolloRESUMEN
The HLA-B5 phenotype was investigated in 235 patients with Behçet's disease and in 100 healthy persons. HLA-B5 was more frequent in the patients (77 vs. 30% p < 0.001, relative risk = 7.8). The frequency of HLA-B5 was higher in patients with genital ulceration than without (82.3 vs. 63%, p < 0.01). Patients with thrombophlebitis showed a less frequent positivity of HLA-B5 antigen than the patients without thrombophlebitis (50 vs. 79.2%, p < 0.02). These results suggest that HLA-B5-related genes not only affect the development of Behçet's disease but also the occurrence of its clinical manifestations.