Microglia, the innate immune cells of the CNS, perform critical inflammatory and noninflammatory functions that maintain normal neural function. For example, microglia clear misfolded proteins, elaborate trophic factors, and regulate and terminate toxic inflammation. In Alzheimer’s disease (AD), however, beneficial microglial functions become impaired, accelerating synaptic and neuronal loss. Better understanding of the molecular mechanisms that contribute to microglial dysfunction is an important objective for identifying potential strategies to delay progression to AD. The inflammatory cyclooxygenase/prostaglandin E2 (COX/PGE2) pathway has been implicated in preclinical AD development, both in human epidemiology studies and in transgenic rodent models of AD. Here, we evaluated murine models that recapitulate microglial responses to Aβ peptides and determined that microglia-specific deletion of the gene encoding the PGE2 receptor EP2 restores microglial chemotaxis and Aβ clearance, suppresses toxic inflammation, increases cytoprotective insulin-like growth factor 1 (IGF1) signaling, and prevents synaptic injury and memory deficits. Our findings indicate that EP2 signaling suppresses beneficial microglia functions that falter during AD development and suggest that inhibition of the COX/PGE2/EP2 immune pathway has potential as a strategy to restore healthy microglial function and prevent progression to AD. 相似文献
AbstractBackground: Auditory steady-state response (ASSR) and click-evoked auditory brain response (c-ABR) have been used for hearing assessment for decades years, the correlation of the two methods and the effects of type and degree of hearing loss (HL) to the correlation in infants younger than 6?months of age are unclear.Objectives: To compare the correlation of ASSR and c-ABR and then to analyse the effects of type and degree of HL on the correlation in infants younger than 6?months of age.Material and methods: Retrospective study comparing ASSR thresholds at various frequencies with c-ABR thresholds. 182 ears from 96 infants were assessed and classified according to types and degrees of HL.Results: The correlation coefficients were: 0.823, 0.864, 0.891, 0.871, 0.908, 0.915 and 0.913 between ASSR thresholds at 0.5, 1, 2, 4, 2–4, 1–2–4, 0.5–1–2–4?kHz and c-ABR thresholds respectively. The correlation coefficients in the group of sensorineural HL (SHL) (r?=?0.763–0.900) were higher than conductive HL (r?=?0.309–0.619) across all frequencies. The coefficients of severe-profound SHL (r?=?0.595–0.790) were higher than mild-moderate SHL (r?=?0.434–0.687) across all frequencies.Conclusions and significance: ASSR was one valuable cross-check measure by providing frequency specific information in auditory assessment. 相似文献
Background: The key factors of inducing drug cravings in persons abstaining from drug use remain a focus of addictions research. Given the accumulating evidences, the scope of cues investigated in the cue-reactivity paradigm has increased considerably. Yet, few studies have examined the effects of the intensity and endurance of different types of cues on their ability to induce craving. This study investigated differences among drug-cue words, negative physiological-cue words, and negative social-cue words in the induction of drug cravings among persons abstaining from heroin.
Methods: The sample consisted of 149 male abstinent heroin abusers from four addiction rehabilitation centers in China. Based on their abstinence lengths, they were labeled as short-term, medium-term, and long-term abstainer participants respectively. All participants completed a stress-imagery task and rated craving by visual analog scale.
Results: There was a significant interaction of cue type and abstinence length. There was no difference on the craving induced by three types of cue words in the short-term group. In the medium-term group, craving induced by negative social-cue words was significantly stronger than that by negative physiological-cue words, but not that by drug-cue words. In the long-term group, the craving induced by negative social-cue words remained the strongest, significantly stronger than that by both drug-cue words and negative physiological-cue words.
Conclusion: Negative social-cue words presented in the current study retain the ability to induce craving in heroin abstainers; this finding suggests that negative social cues encountered under more general circumstances could be a risk factor for relapse. 相似文献