Sarah Yoon

Apolipoprotein E4 is the major genetic risk factor for Alzheimer's disease. ApoE4 has sex-dependent effects, whereby the risk of developing AD is higher in apoE4-expressing females than males. However, the mechanism underlying the sex difference, in relation to apoE4, is unknown. Previous findings indicate that apoE4 causes age-dependent impairments of hilar GABAergic interneurons in female mice, leading to learning and memory deficits. Here, we investigate whether the detrimental effects of apoE4 on hilar GABAergic interneurons are sex-dependent using apoE knock-in mice across different ages. We found that in female apoE-KI mice, there was an age-dependent depletion of hilar GABAergic interneurons, whereby GAD67- or somatostatin-positive-but not NPY- or parvalbumin-positive-interneuron loss was exacerbated by apoE4. Loss of these neuronal populations was correlated with the severity of spatial learning deficits at 16 months of age in female apoE4-KI mice; however, this effect was not observed in female apoE3-KI mice. In contrast, we found an increase in the numbers of hilar GABAergic interneurons with advancing age in male apoE-KI mice, regardless of apoE genotype. Moreover, male apoE-KI mice showed a consistent ratio of hilar inhibitory GABAergic interneurons to excitatory mossy cells approximating 1.5 that is independent of apoE genotype and age, whereas female apoE-KI mice exhibited an age-dependent decrease in this ratio, which was exacerbated by apoE4. Interestingly, there are no apoE genotype effects on GABAergic interneurons in the CA1 and CA3 subregions of the hippocampus as well as the entorhinal and auditory cortexes. These findings suggest that the sex-dependent effects of apoE4 on developing AD is in part attributable to inherent sex-based differences in the numbers of hilar GABAergic interneurons, which is further modulated by apoE genotype. © 2012 Leung et al.

Apolipoprotein E4 is the leading genetic risk factor for Alzheimer's disease, and it has a gene dose-dependent effect on the risk and age of onset of AD. Although apoE4 is primarily produced by astrocytes in the brain, neurons can also produce apoE4 under stress conditions. ApoE4 is known to inhibit neurite outgrowth and spine development in vitro and in vivo, but the potential influence of apoE4's cellular source on dendritic arborization and spine development has not yet been investigated. In this study, we report impairments in dendritic arborization and a loss of spines, especially thin and mushroom spines, in the hippocampus and entorhinal cortex of 19-21-month-old female neuron-specific-enolase -apoE4 and apoE4-knockin mice compared to their respective apoE3-expressing counterparts. In general, NSE-apoE4 mice had more severe and widespread deficits in dendritic arborization as well as spine density and morphology than apoE4-KI mice. The loss of dendritic spines, especially mushroom spines, occurred in NSE-apoE4 mice as early as 7-8 months of age. In contrast, glial fibrillary acidic protein -apoE4 mice, which express apoE4 solely in astrocytes, did not have impairments in their dendrite arborization or spine density and morphology compared to GFAP-apoE3 mice at both ages. These results indicate that the effects of apoE4 on dendrite arborization, spine density, and spine morphology depend critically on its cellular source, with neuronal apoE4 having more detrimental effects than astrocytic apoE4. © 2013 Jain et al.

In pediatric emergency rooms (ERs), social workers must navigate diverse responsibilities including acting as advocates and liaisons between families and multidisciplinary treatment teams, providing compassionate support to families in crisis, and assessing for and reporting any suspicions of child abuse or neglect. These potentially contrasting roles can place social workers at the center of dealing with ethical dilemmas and advocating against ethical violations, such as bias and discrimination toward families. This qualitative study seeks to gain insight into ethical issues commonly encountered in pediatric ERs by exploring the perspectives of 23 social workers at Level 1 trauma centers in the United States. Thematic analysis was used to develop major themes and subthemes related to ethical violations, dilemmas, and best practices in pediatric ERs. Major themes emerged related to unfair treatment of families (with subthemes of bias, discrimination, and compassion fatigue), ethical dilemmas (with subthemes of cultural issues, safety and system issues), and promoting ethical practices (with subthemes of self-awareness, advocacy, and efforts to change the system). This study provides important insights into ethical issues in pediatric ERs as experienced by social workers and can inform efforts to improve the quality and equity of care for all families in pediatric ERs.