Effect of Maternal Age on Offspring Social Behaviour in Drosophila Melanogaster

Aging can be defined as the natural and progressive decline in physiological functioning leading to increased risk for disease and death. Although the effects of age are well characterised, much less work has been done to study whether these detrimental changes can be transmitted to offspring. Advanced parental age has been correlated with higher incidence of neuropsychiatric disorders such as autism in children. As average maternal age increases in North America, it is becoming increasingly relevant to study the effects of maternal and paternal age on offspring social behaviour. We hypothesize that advanced maternal age in Drosophila melanogaster will affect offspring social behaviour as measured in the social space assay. This assay measures the distance to the nearest neighbour (cm) after stable social group formation as an index of social behaviour in the fruit fly. To test the effect of maternal age, we aged Canton-S females to 7, 30, and 50 days corresponding to 100%, 90%, and 50% population survival respectively, and mated them with 7-day old young Canton-S males. Their eggs were collected and allowed to develop into first generation (G1) offspring between the ages of 7–9-days old, which were then separated by sex and tested in the social space assay. We found that female G1 from 50-day old mothers were significantly less social (pD. melanogaster

Sensitive and specific identification by polymerase chain reaction of Eimeria tenella and Eimeria maxima, important protozoan pathogens in laboratory avian facilities

Eimeria tenella and Eimeria maxima are important pathogens causing intracellular protozoa infections in laboratory avian animals and are known to affect experimental results obtained from contaminated animals. This study aimed to find a fast, sensitive, and efficient protocol for the molecular identification of E. tenella and E. maxima in experimental samples using chickens as laboratory avian animals. DNA was extracted from fecal samples collected from chickens and polymerase chain reaction (PCR) analysis was employed to detect E. tenella and E. maxima from the extracted DNA. The target nucleic acid fragments were specifically amplified by PCR. Feces secreting E. tenella and E. maxima were detected by a positive PCR reaction. In this study, we were able to successfully detect E. tenella and E. maxima using the molecular diagnostic method of PCR. As such, we recommended PCR for monitoring E. tenella and E. maxima in laboratory avian facilities

Is therapeutic lying contradictory to person-centred care? Toward understanding the connection.

Aim There is a lack of clarity about therapeutic lying in the context of everyday dementia care. This study provides conceptual clarity on how the term is used and considers the concept in relation to person-centred care. Methods Rodgers’ (Citation1989) evolutionary framework of concept analysis was employed. A systematic multiple database search was conducted and supplemented with snowballing techniques. Data were analysed thematically through an iterative process of constant comparison. Results This study highlighted that therapeutic lying is intended to be used in the person’s best interests for the purpose of doing good. However, its potential for doing harm is also evident. Its use in the literature has increased with the general trend towards becoming more accepted in the discourse. A continuum emerged depending on the degree to which a lie departs from the truth. Emerging guidelines were also evident as to when a lie could or could not be justified. Conclusion The term therapeutic lying, was contrasted with aspects of person-centred care and was found to be problematic. We conclude that there may be more pragmatic ways of constructing language around the care of people with dementia which could be less stigmatising

Genetic deficiency of neuronal RAGE protects against AGE-induced synaptic injury

Synaptic dysfunction and degeneration is an early pathological feature of aging and age-related diseases, including Alzheimer's disease (AD). Aging is associated with increased generation and deposition of advanced glycation endproducts (AGEs), resulting from nonenzymatic glycation (or oxidation) proteins and lipids. AGE formation is accelerated in diabetes and AD-affected brain, contributing to cellular perturbation. The extent of AGEs' involvement, if at all, in alterations in synaptic structure and function is currently unknown. Here we analyze the contribution of neuronal receptor of AGEs (RAGE) signaling to AGE-mediated synaptic injury using novel transgenic neuronal RAGE knockout mice specifically targeted to the forebrain and transgenic mice expressing neuronal dominant-negative RAGE (DN-RAGE). Addition of AGEs to brain slices impaired hippocampal long-term potentiation (LTP). Similarly, treatment of hippocampal neurons with AGEs significantly decreases synaptic density. Such detrimental effects are largely reversed by genetic RAGE depletion. Notably, brain slices from mice with neuronal RAGE deficiency or DN-RAGE are resistant to AGE-induced LTP deficit. Further, RAGE deficiency or DN-RAGE blocks AGE-induced activation of p38 signaling. Taken together, these data show that neuronal RAGE functions as a signal transducer for AGE-induced synaptic dysfunction, thereby providing new insights into a mechanism by which the AGEs–RAGE-dependent signaling cascade contributes to synaptic injury via the p38 MAP kinase signal transduction pathway. Thus, RAGE blockade may be a target for development of interventions aimed at preventing the progression of cognitive decline in aging and age-related neurodegenerative diseases

Synergistic Exacerbation of Mitochondrial and Synaptic Dysfunction and Resultant Learning and Memory Deficit in a Mouse Model of Diabetic Alzheimer’s Disease

Diabetes is considered to be a risk factor in Alzheimer’s disease (AD) pathogenesis. Although recent evidence indicates that diabetes exaggerates pathologic features of AD, the underlying mechanisms are not well understood. To determine whether mitochondrial perturbation is associated with the contribution of diabetes to AD progression, we characterized mouse models of streptozotocin (STZ)-induced type 1 diabetes and transgenic AD mouse models with diabetes. Brains from mice with STZ-induced diabetes revealed a significant increase of cyclophilin D (CypD) expression, reduced respiratory function, and decreased hippocampal long-term potentiation (LTP); these animals had impaired spatial learning and memory. Hyperglycemia exacerbated the upregulation of CypD, mitochondrial defects, synaptic injury, and cognitive dysfunction in the brains of transgenic AD mice overexpressing amyloid-β as shown by decreased mitochondrial respiratory complex I and IV enzyme activity and greatly decreased mitochondrial respiratory rate. Concomitantly, hippocampal LTP reduction and spatial learning and memory decline, two early pathologic indicators of AD, were enhanced in the brains of diabetic AD mice. Our results suggest that the synergistic interaction between effects of diabetes and AD on mitochondria may be responsible for brain dysfunction that is in common in both diabetes and AD

The Summer Of The Pivot: Prioritizing Equity In Remote Instruction Through A Multidisciplinary Community Of Practice Initiative At A Canadian University

This article is about the multidisciplinary Community of Practice (CoP) initiative that was implemented in the summer of 2020- summer of the pivot- at a Canadian post-secondary institution to prepare faculty, staff, and students for remote teaching and learning while navigating pandemic conditions created by COVID-19. The CoP as a case study using Critical Theory as a theoretical framework examines the experiences of a collective group of faculty and staff from different disciplines leading a multidisciplinary university-wide initiative and the implications of the approach for promoting effective pedagogies for teaching and learning remotely. Findings based on feedback from workshop attendees, reflections from the CoP facilitators, and comments forwarded to senior administrators about the impact and the effectiveness of the program indicate positive results. It is recommended that although the CoP initiative was originally conceived as a response to the summer of the pivot, it should become an integral approach to promoting dialogue and innovative strategies to advance equitable practices in higher education by cultivating community networks. The findings serve to continue constructive dialogues and discussions about how universities can transition, pivot, and mobilize innovatively and creatively to prioritize equitable teaching and learning conditions that challenge the status quo. This requires a long-term commitment by higher education institutions to break away from historically normalized practices and invest in innovative ways to identify and meet the needs of various stakeholders

Oxidative stress-mediated activation of extracellular signal-regulated kinase contributes to mild cognitive impairment-related mitochondrial dysfunction

Mild cognitive impairment (MCI) occurs during the pre-dementia stage of Alzheimer’s disease (AD) and is characterized by a decline in cognitive abilities that frequently represents a transition between normal cognition and AD dementia. Its pathogenesis is not well understood. Here, we demonstrate the direct consequences and potential mechanisms of oxidative stress, mitochondrial dynamic and functional defects in MCI-derived mitochondria. Using cytoplasmic hybrid (cybrid) cell model in which mitochondria from MCI or age-matched non-MCI subjects were incorporated into a human neuronal cell line depleted of endogenous mitochondrial DNA, we evaluated the mitochondrial dynamics and functions, as well as the role of oxidative stress in the resultant cybrid lines. We demonstrated increased expression levels of mitofusin 2 (Mfn2) is markedly induced by oxidative stress in MCI-derived mitochondria along with aberrant mitochondrial functions. Inhibition of oxidative stress rescues MCI-impaired mitochondrial fusion/fission balance as shown by the suppression of Mfn2 expression, attenuation of abnormal mitochondrial morphology and distribution, and improvement in mitochondrial function. Furthermore, blockade of MCI related stress-mediated activation of extracellular signal-regulated kinase (ERK) signaling not only attenuates aberrant mitochondrial morphology and function but also restores mitochondrial fission and fusion balance, in particular inhibition of overexpressed Mfn2. Our results provide new insights into the role of the oxidative stress-ERK-Mfn2 signal axis in MCI-related mitochondrial abnormalities, indicating that the MCI phase may be targetable for the development new therapeutic approaches that improve mitochondrial function in age-related neurodegeneration

Inhibition of ERK-DLP1 signaling and mitochondrial division alleviates mitochondrial dysfunction in Alzheimer's disease cybrid cell

Mitochondrial dysfunction is an early pathological feature of Alzheimer’s disease (AD). The underlying mechanisms and strategies to repair it remain unclear. Here, we demonstrate for the first time the direct consequences and potential mechanisms of mitochondrial functional defects associated with abnormal mitochondrial dynamics in AD. Using cytoplasmic hybrid (cybrid) neurons with incorporated platelet mitochondria from AD and age-matched non-AD human subjects into mitochondrial DNA (mtDNA)-depleted neuronal cells, we observed that AD cybrid cells had significant changes in morphology and function; such changes associate with altered expression and distribution of dynamin-like protein (DLP1) and mitofusin 2 (Mfn2). Treatment with antioxidant protects against AD mitochondria-induced extracellular signal-regulated kinase (ERK) activation and mitochondrial fission-fusion imbalances. Notably, inhibition of ERK activation not only attenuates aberrant mitochondrial morphology and function but also restores the mitochondrial fission and fusion balance. These effects suggest a role of oxidative stress-mediated ERK signal transduction in modulation of mitochondrial fission and fusion events. Further, blockade of the mitochondrial fission protein DLP1 by a genetic manipulation with a dominant negative DLP1 (DLP1K38A), its expression with siRNA-DLP1, or inhibition of mitochondrial division with mdivi-1 attenuates mitochondrial functional defects observed in AD cybrid cells. Our results provide new insights into mitochondrial dysfunction resulting from changes in the ERK-fission/fusion (DLP1) machinery and signaling pathway. The protective effect of mdivi-1 and inhibition of ERK signaling on maintenance of normal mitochondrial structure and function holds promise as a potential novel therapeutic strategy for AD