Hypoxia is a condition characterized by insufficient tissue oxygenation, which results in impaired oxidative energy production. A reduction in cellular oxygen levels induces the stabilization of hypoxia inducible factor α (HIF-1α), master regulator of the molecular response to hypoxia, involved in maintaining cellular homeostasis and driving hypoxic adaptation through the control of gene expression. Due to its high energy requirement, the brain is particularly vulnerable to oxygen shortage. Thus, hypoxic injury can cause significant metabolic changes in neural cell populations, which are associated with neurodegeneration. Recent evidence suggests that regulating HIF-1α may ameliorate the cellular damage in neurodegenerative diseases. Indeed, the hypoxia/HIF-1α signaling pathway has been associated to several processes linked to Parkinson’s disease (PD) including gene mutations, risk factors and molecular pathways such as mitochondrial dysfunction, oxidative stress and protein degradation impairment. This review will explore the impact of hypoxia and HIF-1α signaling on these specific molecular pathways that influence PD development and will evaluate different novel neuroprotective strategies involving HIF-1α stabilization.
: The effect of the neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) was investigated in mouse N2a neuroblastoma cells, induced to differentiate by serum withdrawal and addition of dibutyryl cyclic AMP, over a 24‐h period. Addition of MPTP (10 μM) during differentiation caused a change in cell morphology characterised by an inhibition of axon outgrowth, in the absence of cell death. Biochemical characterisation by western blotting revealed that MPTP had no significant effects on the levels of actin, α‐tubulin, or total heavy‐chain neurofilament (NF‐H). However, NF‐H phosphorylation appeared to increase following MPTP treatment when blots were probed with the phosphorylation state‐specific antibodies RMd09 and Ta51. In addition, indirect immunofluorescence analysis revealed an accumulation of phosphorylated NF‐H in the cell perikaryon, suggesting that altered NF‐H distribution was associated with the observed effects of MPTP on cell morphology. These changes may represent a useful in vitro marker of MPTP neurotoxicity within a simple differentiating neuronal cell model system.
30 January 2006 in Journal of Neuroscience Research
Development of key practical skills is fundamental to bioscience courses in higher education. With limitations on access to laboratory time due to the COVID-19 pandemic, a “Bioskills at home” kit was developed to create opportunities for first year undergraduate students to develop these skills using online support resources to guide their activities and build communities of learning. Equipment and activities in this kit enabled students to practice key skills such as pipetting, data handling, experimental design and microscopy, as well as build an online peer learning community through the use of discussion boards and microscopy competitions that encouraged students to explore their local environment. Students who engaged with these activities reported increased confidence in key practical skills. Practical assessment of skills showed that that there was no reduction in the proportion of students who succeeded in achieving the pipetting learning objective compared to previous years, despite a significantly reduced on-campus provision. Although the celebration event to choose the microscopy competition winners was well attended, there was limited use of the discussion boards by students to build a community of learning during the term. Refinement of this initiative will focus on providing greater scaffolding to encourage greater engagement with activities and enhance community building.