RESUMO
The liver X receptor agonist, GW3965, improves cognition in Alzheimer's disease (AD) mouse models. Here, we determined if short-term GW3965 treatment induces changes in the DNA methylation state of the hippocampus, which are associated with cognitive improvement. Twenty-four-month-old triple-transgenic AD (3xTg-AD) mice were treated with GW3965 (50 mg/kg/day for 6 days). DNA methylation state was examined by modified bisulfite conversion and hybridization on Illumina Infinium Methylation BeadChip 450 k arrays. The Morris water maze was used for behavioral analysis. Our results show in addition to improvement in cognition methylation changes in 39 of 13,715 interrogated probes in treated 3xTg-AD mice compared with untreated 3xTg-AD mice. These changes in methylation probes include 29 gene loci. Importantly, changes in methylation status were mainly from synapse-related genes (SYP, SYN1, and DLG3) and neurogenesis-associated genes (HMGB3 and RBBP7). Thus, our results indicate that liver X receptors (LXR) agonist treatment induces rapid changes in DNA methylation, particularly in loci associated with genes involved in neurogenesis and synaptic function. Our results suggest a new potential mechanism to explain the beneficial effect of GW3965.
Assuntos
Doença de Alzheimer/metabolismo , Benzoatos/farmacologia , Benzilaminas/farmacologia , Metilação de DNA/efeitos dos fármacos , Neurogênese , Receptores Nucleares Órfãos/agonistas , Sinapses/efeitos dos fármacos , Doença de Alzheimer/genética , Animais , Feminino , Proteína HMGB3/genética , Proteína HMGB3/metabolismo , Receptores X do Fígado , Camundongos , Proteínas Qa-SNARE/genética , Proteínas Qa-SNARE/metabolismo , Proteína 7 de Ligação ao Retinoblastoma/genética , Proteína 7 de Ligação ao Retinoblastoma/metabolismo , Sinapses/metabolismo , Sinaptofisina/genética , Sinaptofisina/metabolismoRESUMO
The Sahara experienced several humid episodes during the late Quaternary, associated with the development of vast fluvial networks and enhanced freshwater delivery to the surrounding ocean margins. In particular, marine sediment records off Western Sahara indicate deposition of river-borne material at those times, implying sustained fluvial discharges along the West African margin. Today, however, no major river exists in this area; therefore, the origin of these sediments remains unclear. Here, using orbital radar satellite imagery, we present geomorphological data that reveal the existence of a large buried paleodrainage network on the Mauritanian coast. On the basis of evidence from the literature, we propose that reactivation of this major paleoriver during past humid periods contributed to the delivery of sediments to the Tropical Atlantic margin. This finding provides new insights for the interpretation of terrigenous sediment records off Western Africa, with important implications for our understanding of the paleohydrological history of the Sahara.
RESUMO
For the study on boron neutron capture therapy, the whole-body sections of tumor-bearing mice infused with 10B attached to CR-39 plastic track detectors were exposed to thermal and cold neutron beams. Neutron capture autoradiographic images obtained by the cold neutron irradiation were extremely superior in quality to those of the thermal neutron beams. From the autoradiographic images, the 10B reaction dose of the neutron-induced particles was estimated using the differential LET distribution.
