Mitochondrial Superoxide Contributes to Blood Flow and Axonal Transport Deficits in the Tg2576 Mouse Model of Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disease characterized by the progressive decline in cognitive functions and the deposition of aggregated amyloid beta (Abeta) into senile plaques and the protein tau into tangles. In addition, a general state of oxidation has long been known to be a major hallmark of the disease. What is not known however, are the mechanisms by which oxidative stress contributes to the pathology of AD.In the current study, we used a mouse model of AD and genetically boosted its ability to quench free radicals of specific mitochondrial origin. We found that such manipulation conferred to the AD mice protection against vascular as well as neuronal deficits that typically affect them. We also found that the vascular deficits are improved via antioxidant modulation of the endothelial nitric oxide synthase, an enzyme primarily responsible for the production of nitric oxide, while neuronal deficits are improved via modulation of the phosphorylation status of the protein tau, which is a neuronal cytoskeletal stabilizer.These findings directly link free radicals of specific mitochondrial origin to AD-associated vascular and neuronal pathology

Gene Expression Analysis of Forskolin Treated Basilar Papillae Identifies MicroRNA181a as a Mediator of Proliferation

Auditory hair cells spontaneously regenerate following injury in birds but not mammals. A better understanding of the molecular events underlying hair cell regeneration in birds may allow for identification and eventually manipulation of relevant pathways in mammals to stimulate regeneration and restore hearing in deaf patients.Gene expression was profiled in forskolin treated (i.e., proliferating) and quiescent control auditory epithelia of post-hatch chicks using an Affymetrix whole-genome chicken array after 24 (n = 6), 48 (n = 6), and 72 (n = 12) hours in culture. In the forskolin-treated epithelia there was significant (p<0.05; >two-fold change) upregulation of many genes thought to be relevant to cell cycle control and inner ear development. Gene set enrichment analysis was performed on the data and identified myriad microRNAs that are likely to be upregulated in the regenerating tissue, including microRNA181a (miR181a), which is known to mediate proliferation in other systems. Functional experiments showed that miR181a overexpression is sufficient to stimulate proliferation within the basilar papilla, as assayed by BrdU incorporation. Further, some of the newly produced cells express the early hair cell marker myosin VI, suggesting that miR181a transfection can result in the production of new hair cells.These studies have identified a single microRNA, miR181a, that can cause proliferation in the chicken auditory epithelium with production of new hair cells

Does Self-Compassion Protect Adolescents from Stress?

The aim of this study was to determine whether adolescents who were high in self-compassion self-reported different levels of emotional wellbeing than adolescents who were low in self-compassion, and to determine whether those high in self-compassion responded differently under a lab social stressor than those low in self-compassion. In a lab setting, participants (age 13–18; n = 28) completed the Trier Social Stress Test (TSST) and physiological stress was assessed via salivary cortisol, heart rate, blood pressure, and heart rate variability at baseline, during the TSST, and during recovery. After completing the lab protocol, an email was sent to participants that provided a link to an online survey which was composed of emotional wellbeing measures including perceived stress, life satisfaction, positive and negative affect. After conducting repeated measure ANOVAS to determine that the TSST induced a significant stress response, the sample was split at the median of self-compassion. T tests were conducted to determine meaningful differences (Hedges’ g > .20) between the groups. Findings indicated that those in the high self-compassion group (≥the median) self-reported greater emotional wellbeing than those in the low self-compassion group (<the median). Overall, those in the high self-compassion group also had a lower physiologic stress response when exposed to the TSST than those in the low self-compassion group. Regression analyses were also conducted; baseline self-compassion predicted self-reported emotional wellbeing, but did not predict physiological response to the TSST. Findings support the potential buffering effect that self-compassion may have in protecting adolescents from social stressors; yet more research needs to be conducted in larger samples to confirm and replicate these findings