Changes in insulin and insulin signaling in Alzheimer\u27s disease: Cause or consequence?

Individuals with type 2 diabetes have an increased risk for developing Alzheimer’s disease (AD), although the causal relationship remains poorly understood. Alterations in insulin signaling (IS) are reported in the AD brain. Moreover, oligomers/fibrils of amyloid-β (Aβ) can lead to neuronal insulin resistance and intranasal insulin is being explored as a potential therapy for AD. Conversely, elevated insulin levels (ins) are found in AD patients and high insulin has been reported to increase Aβ levels and tau phosphorylation, which could exacerbate AD pathology. Herein, we explore whether changes in ins and IS are a cause or consequence of AD

Situated Learning and On-Farm Apprenticeships: Political Implications of Negotiating Apprentice Identity

By drawing upon the tradition of situated and activity perspectives of adult learning, this mixed methods study underscores the sociocultural and politicized processes by which farmer/learners negotiate apprentice identity. Our findings offer implications for the formation of equitable apprenticeship learning experiences and career pathways

Learning Through On-Farm Apprenticeships: Labor Identities and Sociocultural Reproduction within Alternative Agrifood Movements

On-farm apprenticeship is a site of sociocultural learning for beginning farmers, and also for identity politics, mediated by social movement learning processes. This critical ethnographic case study examines this activity

The role of attenuated astrocyte activation in infantile neuronal Ceroid Lipofuscinosis

Infantile neuronal ceroid lipofuscinosis (INCL) is an inherited neurodegenerative disorder affecting the CNS during infancy. INCL is caused by mutations in the CLN1 gene that leads to a deficiency in the lysosomal hydrolase, palmitoyl protein thioesterase (PPT1). A murine model of INCL, the PPT1(−/−) mouse, is an accurate phenocopy of the human disease. The first pathological change observed in the PPT1(−/−) brain is regional areas of GFAP upregulation, which predicts future areas of neurodegeneration. We hypothesized that preventing GFAP upregulation in reactive astrocytes will alter the CNS disease. To test this hypothesis, we generated mice simultaneously carrying null mutations in the GFAP, Vimentin, and PPT1 genes (GFAP(−/−)Vimentin(−/−)PPT1(−/−)). Although the clinical and pathological features of the GFAP(−/−)Vim(−/−)PPT1(−/−) mice are similar to INCL, the disease appears earlier and progresses more rapidly. One mechanism underlying this accelerated phenotype is a profound neuroinflammatory response within the CNS. Thus, our data identify a protective role for intermediate filament upregulation during astrocyte activation in INCL, a model of chronic neurodegeneration

Model of Community, Local, and Regional Food Systems Extension Programming

Community, local, and regional food systems (CLRFS) programming reflects important issues and priorities that intersect with Extension and the sustainability of our food system. CLRFS programming in Extension, however, is still developing slowly while food movements grow nationally. This article describes a CLRFS model and complementary process for conducting listening sessions with Extension professionals and community leaders to develop and enhance CLRFS programming to address critical food system needs. A recommendation for Cooperative Extension is that such a tool may aid CLRFS program potential as an integrated “food, farm, and health” approach for community-level application

The Journey to R4D: An institutional history of an Australian Initiative on Food Security in Africa

Internal Revie

The effects of peripheral and central high insulin on brain insulin signaling and amyloid-β in young and old APP/PS1 mice

Hyperinsulinemia is a risk factor for late-onset Alzheimer's disease (AD). In vitro experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but in vivo experiments are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving APP(swe)/PS1(dE9) transgenic mice. Both a postprandial and supraphysiological insulin clamp significantly increased interstitial fluid (ISF) and plasma Aβ compared with controls. We could detect no increase in brain, ISF, or CSF insulin or brain insulin signaling in response to peripheral hyperinsulinemia, despite detecting increased signaling in the muscle. Next, we delivered insulin directly into the hippocampus of young APP/PS1 mice via reverse microdialysis. Brain tissue insulin and insulin signaling was dose-dependently increased, but ISF Aβ was unchanged by central insulin administration. Finally, to determine whether peripheral and central high insulin has differential effects in the presence of significant amyloid pathology, we repeated these experiments in older APP/PS1 mice with significant amyloid plaque burden. Postprandial insulin clamps increased ISF and plasma Aβ, whereas direct delivery of insulin to the hippocampus significantly increased tissue insulin and insulin signaling, with no effect on Aβ in old mice. These results suggest that the brain is still responsive to insulin in the presence of amyloid pathology but increased insulin signaling does not acutely modulate Aβ in vivo before or after the onset of amyloid pathology. Peripheral hyperinsulinemia modestly increases ISF and plasma Aβ in young and old mice, independent of neuronal insulin signaling. SIGNIFICANCE STATEMENT The transportation of insulin from blood to brain is a saturable process relevant to understanding the link between hyperinsulinemia and AD. In vitro experiments have found direct connections between high insulin and extracellular Aβ, but these mechanisms presume that peripheral high insulin elevates brain insulin significantly. We found that physiological hyperinsulinemia in awake, behaving mice does not increase CNS insulin to an appreciable level yet modestly increases extracellular Aβ. We also found that the brain of aged APP/PS1 mice was not insulin resistant, contrary to the current state of the literature. These results further elucidate the relationship between insulin, the brain, and AD and its conflicting roles as both a risk factor and potential treatment

Identifying experiences of supportive care of children and young people affected by kidney failure: a qualitative systematic review.

Children and young people affected by kidney failure experience complexities in their care. Little is known about the unique needs of this young patient population group living with a long-term condition. A meta-aggregation of all qualitative studies was conducted to identify experiences of supportive care among children and young people living with kidney failure. A systematic review of qualitative studies was conducted following the Joanna Briggs Institute meta-aggregation method. This review has been reported according to the PRISMA statement guidelines. Six electronic databases (CINAHL, Cochrane Library, MEDLINE, Proquest, PsycINFO, and Scopus) were comprehensively searched by an expert systematic review librarian using keywords and subject headings, from inception to September 2022. All studies were accessed using a predetermined inclusion and exclusion criteria. Methodological quality assessment and data extraction performed. Qualitative findings accompanied by illustrative quotes from included studies were extracted and grouped into categories which created the overall synthesised findings. A total of 34 studies were included in this review representing a total of 613 children and young people affected by kidney failure. There was a total of 190 findings which created 13 categories representing experiences of supportive care. The meta-aggregation developed five synthesised findings namely: 'physical needs', 'information and technology', 'treatment and healthcare', 'social needs' and 'psychological impacts'. This systematic review identified that children and young people affected by kidney failure can experience a range of unmet supportive care needs in routine clinical services. Kidney failure impacted children and young people's self-identify, social and peer networks, introduced daily practical needs because of inherent physical and psychological burden due to the failure and associated treatments. Despite improvements in the medical management of kidney failure in children and young people, further attention is needed to optimise supported self-management in this young patient group