Optimization of a multielectrode array (MEA)-based approach to study the impact of Aβ on the SH-SY5Y cell line

The human brain stores, integrates, and transmits information recurring to millions of neurons, interconnected by countless synapses. Though neurons communicate through chemical signaling, information is coded and conducted in the form of electrical signals. Neuroelectrophysiology focus on the study of this type of signaling. Both intra and extracellular approaches are used in research, but none holds as much potential in high-throughput screening and drug discovery, as extracellular recordings using multielectrode arrays (MEAs). MEAs measure neuronal activity, both in vitro and in vivo. Their key advantage is the capability to record electrical activity at multiple sites simultaneously. Alzheimer’s disease (AD) is the most common neurodegenerative disease and one of the leading causes of death worldwide. It is characterized by neurofibrillar tangles and aggregates of amyloid-β (Aβ) peptides, which lead to the loss of synapses and ultimately neuronal death. Currently, there is no cure and the drugs available can only delay its progression. In vitro MEA assays enable rapid screening of neuroprotective and neuroharming compounds. Therefore, MEA recordings are of great use in both AD basic and clinical research. The main aim of this thesis was to optimize the formation of SH-SY5Y neuronal networks on MEAs. These can be extremely useful for facilities that do not have access to primary neuronal cultures, but can also save resources and facilitate obtaining faster high-throughput results to those that do. Adhesion-mediating compounds proved to impact cell morphology, viability and exhibition of spontaneous electrical activity. Moreover, SH-SY5Y cells were successfully differentiated and demonstrated acute effects on neuronal function after Aβ addition. This effect on electrical signaling was dependent on Aβ oligomers concentration. The results here presented allow us to conclude that the SH-SY5Y cell line can be successfully differentiated in properly coated MEAs and be used for assessing acute Aβ effects on neuronal signaling.

Role of climate on barn owls road-kill likelihood and the effect on population viability in future climate change

Roads represent a new source of mortality due to animal-vehicle risk of collision threatening log-term populations’ viability. Risk of road-kill depends on species sensitivity to roads and their specific life-history traits. The risk of road mortality for each species depends on the characteristics of roads and bioecological characteristics of the species. In this study we intend to know the importance of climatic parameters (temperature and precipitation) together with traffic and life history traits and understand the role of drought in barn owl population viability, also affected by road mortality in three scenarios: high mobility, high population density and the combination of previous scenarios (mixed) (Manuscript). For the first objective we correlated the several parameters (climate, traffic and life history traits). We used the most correlated variables to build a predictive mixed model (GLMM) the influence of the same. Using a population model we evaluated barn owl population viability in all three scenarios. Model revealed precipitation, traffic and dispersal have negative relationship with road-kills, although the relationship was not significant. Scenarios showed different results, high mobility scenario showed greater population depletion, more fluctuations over time and greater risk of extinction. High population density scenario showed a more stable population with lower risk of extinction and mixed scenario showed similar results as first scenario. Climate seems to play an indirect role on barn owl road-kills, it may influence prey availability which influences barn owl reproductive success and activity. Also, high mobility scenario showed a greater negative impact on viability of populations which may affect their ability and resilience to other stochastic events. Future research should take in account climate and how it may influence species life cycles and activity periods for a more complete approach of road-kills. Also it is important to make the best mitigation decisions which might include improving prey quality habitat.