Exacerbated pathology of viral encephalitis in mice with central nervous system-specific autoantibodies

We examine here the outcome of viral encephalomyelitis [mouse hepatitis virus (MHV) A59, Theiler's encephalomyelitis virus, and Coxsackievirus B3] in mice with autoantibodies to a central nervous system (CNS)-specific antigen, myelin oligodendrocyte glycoprotein, that usually develop no clinical disease. Morbidity and mortality of the acute viral CNS disease was augmented by the presence of the autoantibodies in all three viral infections. Transfer of serum containing the autoantibodies at the time of infection with MHV was sufficient to reproduce the exacerbated disease. The presence of the autoantibodies was found to result in increased infiltration of mononuclear cells into the brain. Early demyelination was severely augmented in brains and spinal cords of MHV-infected mice with CNS-specific autoantibodies. The antibody-mediated exacerbation was shown to be independent of the complement system but to require expression of Fc receptors, because it was observed in C'-3-deficient but not in Fc receptor-deficient mice. Our study illustrates the possibility that infections can lead to much more profound immunopathology in the presence of an otherwise latent autoimmune condition.     

Interferon-gamma and tumor necrosis factor-alpha regulate amyloid-beta plaque deposition and beta-secretase expression in Swedish mutant APP transgenic mice

Reactive astrocytes and microglia in Alzheimer's disease surround amyloid plaques and secrete proinflammatory cytokines that affect neuronal function. Relationship between cytokine signaling and amyloid-beta peptide (Abeta) accumulation is poorly understood. Thus, we generated a novel Swedish beta-amyloid precursor protein mutant (APP) transgenic mouse in which the interferon (IFN)-gamma receptor type I was knocked out (APP/GRKO). IFN-gamma signaling loss in the APP/GRKO mice reduced gliosis and amyloid plaques at 14 months of age. Aggregated Abeta induced IFN-gamma production from co-culture of astrocytes and microglia, and IFN-gamma elicited tumor necrosis factor (TNF)-alpha secretion in wild type (WT) but not GRKO microglia co-cultured with astrocytes. Both IFN-gamma and TNF-alpha enhanced Abeta production from APP-expressing astrocytes and cortical neurons. TNF-alpha directly stimulated beta-site APP-cleaving enzyme (BACE1) expression and enhanced beta-processing of APP in astrocytes. The numbers of reactive astrocytes expressing BACE1 were increased in APP compared with APP/GRKO mice in both cortex and hippocampus. IFN-gamma and TNF-alpha activation of WT microglia suppressed Abeta degradation, whereas GRKO microglia had no changes. These results support the idea that glial IFN-gamma and TNF-alpha enhance Abeta deposition through BACE1 expression and suppression of Abeta clearance. Taken together, these observations suggest that proinflammatory cytokines are directly linked to Alzheimer's disease pathogenesis.     

Dynamic changes in conjunctival dendritic cell numbers, anatomical position and phenotype during experimental allergic conjunctivitis

Dendritic cells (DCs) are a subset of antigen-presenting cells (APCs) that are involved in the initiation and control of the immune response to antigens present at the interface with the environment. A limited number of groups have studied DCs in human and animal conjunctiva but no data is available concerning the different DC subsets present in the conjunctival tissue. The aims of this study are to characterize the phenotypes and numbers of DCs present in the murine model of allergic conjunctivitis using the technique of immunohistochemistry so as to aid the understanding of the mechanisms involved in allergic eye disease. A double immunofluorescence method was used to analyze the phenotypic distribution and density of DC subsets in the mouse conjunctival tissues of the allergic model using a panel of antibodies: CD11c, as a general marker of DCs, coupled with another DC subset marker such as Langerin for Langerhans cells (LCs), CD11b for myeloid DCs (mDCs) and mPDCA-1 for plasmacytoid DCs (pDCs). In the na?ve conjunctiva, mDCs were consistently detected in the subepithelial layer and substantia propria. In the epithelium and the subepithelial layer, very few LCs and virtually no pDCs were observed. Following allergen challenge, there was a marked influx of mDCs and pDCs, but no LCs, into the subepithelial layer and throughout the substantia propria. These results indicate that conjunctival DC subsets may play an important role in the immune-regulatory processes involved in the inflammatory component of allergic conjunctivitis.     

Alterations in presenilin 1 processing by amyloid-β peptide in the rat retina

Accumulating evidence indicates that mutations in the presenilin 1 (PS1) gene are responsible for most cases of familial Alzheimer’s disease (AD). Although its biological functions are not yet fully understood, it appears that PS1 plays a role in the processing and trafficking of the amyloid precursor protein (APP). However, little is known about factors that are involved in regulating the metabolism of PS1 especially in relation to AD pathology. In this study, we have examined the effect of optic nerve crush, intravitreal injection of the inflammatory agent lipopolysaccharide (LPS) or injection of amyloid β_1-42 (Aβ_1-42) on the expression and processing of PS1 in the rat retina. We found that 48 h after injection of Aβ_1-42 there was a dramatic alteration in the banding pattern of PS1 on Western blots, as indicated by marked changes in the levels of expression of some of its C- and N-terminal fragments in retinal homogenates. These results suggest an Aβ_1-42-induced potentiation of a non-specific stress-related but inflammation-independent alteration of processing of PS1 in this in vivo model.     

From “Bibbid-Bobbidi-Boo” to Scrooge: an update and comparative analysis of the portrayal of older characters in recent Disney animated films

Disney animated films continue to be a medium viewed by millions of young audiences across the world. As such, Disney content messages – which are often repeatedly viewed by children – and correlating implications should frequently be assessed. The objective for this investigation was to evaluate the portrayal of older adults in more recent Disney animated films (from 2004 to 2016) to provide both an update and comparative analysis to previous explorations. Results suggest comparable findings: we note a similarity in the overall negative portrayal of older characters in recent Disney animated films compared to previous films. Furthermore, we observed a decrease in “neutral” or general aging qualities, as well as a slight increase in the number of older adults depicted as “the villain.” Implications and observations are offered in efforts to improve ageist representations, particularly in a medium that is exceptionally prevalent in the lives of many young people.     

Prevalence and determinants of low protein intake in very old adults: insights from the Newcastle 85+ Study

Purpose

The very old (aged ≥ 85 years), fastest growing age group in most western societies, are at especially high risk of muscle mass and strength loss. The amount, sources and timing of protein intake may play important roles in the aetiology and management of sarcopenia. This study investigated the prevalence and determinants of low protein intake in 722 very old adults participating in the Newcastle 85+ Study.

Methods

Protein intake was estimated with 2 × 24-h multiple pass recalls (24 h-MPR) and contribution (%) of food groups to protein intake was calculated. Low protein intake was defined as intake < 0.8 g of protein per adjusted body weight per day. A backward stepwise multivariate linear regression model was used to explore socioeconomic, health and lifestyle predictors of protein intake.

Results

Twenty-eight percent (n = 199) of the community-living very old in the Newcastle 85+ Study had low protein intake. Low protein intake was less likely when participants had a higher percent contribution of meat and meat products to total protein intake (OR 0.97, 95% CI 0.95, 1.00) but more likely with a higher percent contribution of cereal and cereal products and non-alcoholic beverages. Morning eating occasions contributed more to total protein intake in the low than in the adequate protein intake group (p < 0.001). Being a woman (p < 0.001), having higher energy intake (p < 0.001) and higher tooth count (p = 0.047) was associated with higher protein intake in adjusted models.

Conclusion

This study provides novel evidence on the prevalence of low protein intake, diurnal protein intake patterns and food group contributors to protein intake in the very old.

     

Exploring Antipsychotic Prescribing Behaviors for Nursing Home Residents With Dementia: A Qualitative Study

Objectives

Caution is advised when prescribing antipsychotics to people with dementia. This study explored the determinants of appropriate, evidence-based antipsychotic prescribing behaviors for nursing home residents with dementia, with a view to informing future quality improvement efforts and behavior change interventions.