Search

Cognitive impairment is a major feature of Alzheimer's disease and is accompanied by β-amyloid (Aβ) deposition. Transgenic animal models that overexpress Aβ exhibit learning and memory impairments, but neuronal degeneration is not a consistent characteristic. We report that levels of Aβ-(1–42), which do not compromise the survival of cortical neurons, may indeed interfere with functions critical for neuronal plasticity. Pretreatment with Aβ-(1–42), at sublethal concentrations, resulted in a suppression of cAMP-response element-binding protein (CREB) phosphorylation, induced by exposure to either 30 mmKCl or 10 μmN-methyl-d-aspartate. The effects of Aβ-(1–42) seem to involve mechanisms unrelated to degenerative changes, since Aβ-(25–35), a toxic fragment of Aβ, at sublethal concentrations did not interfere with activity-dependent CREB phosphorylation. Furthermore, caspase inhibitors failed to counteract the Aβ-(1–42)-evoked suppression of CREB activation. Aβ-(1–42) also interfered with events downstream of activated CREB. The Aβ-(1–42) treatment suppressed the activation of the cAMP response element-containing brain-derived neurotrophic factor (BDNF) exon III promoter and the expression of BDNF exon IIII mRNA induced by neuronal depolarization. In view of the critical role of CREB and BDNF in neuronal plasticity, including learning and memory, the observations indicate a novel pathway through which Aβ may interfere with neuronal functions and contribute to cognitive deficit in Alzheimer's disease before the stage of massive neuronal degeneration.

Research studies clearly indicate that age‐related changes in cellular and tissue function are linked to decreases in the anabolic hormones, growth hormone and insulin‐like growth factor (IGF)‐1. Although there has been extensive research on the effects of these hormones on bone and muscle mass, their effect on cerebrovascular and brain ageing has received little attention. We have also observed that in response to moderate calorie restriction (a treatment that increases mean and maximal lifespan by 30–40%), age‐related decreases in growth hormone secretion are ameliorated (despite a decline in plasma levels of IGF‐1) suggesting that some of the effects of calorie restriction are mediated by modifying the regulation of the growth hormone/IGF‐1 axis. Recently, we have observed that microvascular density on the surface of the brain decreases with age and that these vascular changes are ameliorated by moderate calorie restriction. Analysis of cerebral blood flow paralleled the changes in vasculature in both groups. Administration of growth hormone for 28 d was also found to increase microvascular density in aged animals and further analysis indicated that the cerebral vasculature is an important paracrine source of IGF‐1 for the brain. In subsequent studies, administration of GHRH (to increase endogenous release of growth hormone) or direct administration of IGF‐1 was shown to reverse the age‐related decline in spatial working and reference memory. Similarly, antagonism of IGF‐1 action in the brains of young animals impaired both learning and reference memory. Investigation of the mechanisms of action of IGF‐1 suggested that this hormone regulates age‐related alterations in NMDA receptor subtypes (e.g. NMDAR2A and R2B). The beneficial role of growth hormone and IGF‐1 in ameliorating vascular and brain ageing are counterbalanced by their well‐recognised roles in age‐related pathogenesis. Although research in this area is still evolving, our results suggest that decreases in growth hormone and IGF‐1 with age have both beneficial and deleterious effects. Furthermore, part of the actions of moderate calorie restriction on tissue function and lifespan may be mediated through alterations in the growth hormone/IGF‐1 axis.

The Alzheimer disease-associated β-amyloid peptide has been shown to induce apoptotic neuronal death. In the present study, we test the hypothesis that the apoptotic pathway activated by β-amyloid is similar to the pathway activated by the Fas/TNFR family of death receptors, which requires caspase-8 activity and adaptor proteins such as FADD. We demonstrate that the selective caspase-8 inhibitor IETD-fmk blocks neuronal death induced by β-amyloid. Furthermore, using viral-mediated gene delivery, we show that neurons expressing dominant-negative FADD are protected from apoptosis induced by β-amyloid. Together these results indicate that the apoptotic pathway activated by β-amyloid requires both caspase-8 activity and FADD. These findings further support the hypothesis that β-amyloid might initiate apoptosis by cross-linking death receptors of the Fas/TNFR family.

The Pacific food system has become progressively more integrated into global food regimes. This integration has had impacts on availability and consumption of food, population health, and vulnerability to external drivers. We describe major elements of the contemporary food system to provide a foundation for analysis of food system transitions and public health outcomes. Although crop production has doubled in the last fifty years, it has not kept pace with population growth. This deficit is increasingly filled by imported foods, particularly staples, meat and sugar. The burden of malnutrition and poor health outcomes are increasingly apparent. We propose seeds for transitioning the Pacific food system to a hybrid form that supports historical continuity with healthy regionally-produced food.

The 2009-2010 American Association of Colleges of Pharmacy (AACP) Council of Faculties Faculty Affairs Committee reviewed published literature assessing the scope and outcomes of faculty development for tenure and promotion. Relevant articles were identified via a PubMed search, review of pharmacy education journals, and identification of position papers from major healthcare professions academic organizations. While programs intended to enhance faculty development were described by some healthcare professions, relatively little specific to pharmacy has been published and none of the healthcare professions have adequately evaluated the impact of various faculty-development programs on associated outcomes.

Objective.To implement an integrated module on death and dying into a 15-week bioethics course and determine whether it increased student pharmacists’ empathy.