Oligomeric Amyloid-b Peptide Uptake by Microglia Cells Grown on Substrates of Different Elasticity
thesisposted on 31.10.2017, 00:00 by Cecilia Teresa Brambilla Pisoni
Alzheimer’s disease (AD) is a neurodegenerative pathology, that is estimated to affect 13.2 million American by 2050 if no preventive therapies could be found; it has become an urgent research priority in the last years, to mitigate its impact on the society. Recently, some evidence has shown that alterations in the mechanical properties of the brain tissue are implicated in the pathology. Thanks to new bio-imaging technologies, it is possible to study non-invasively the morphological changes in AD brain and correlate these alterations with cognitive performance. The mechanical properties of AD brain have been measured by magnetic resonance elastography (MRE) and some studies have shown that the stiffness of the human brain tissue decreases in AD subjects and the reduction in the elasticity is correlated with the AD severity. As it is well known, the microenvironment surrounding the cells has several effects on the cell functions and proliferation. The main objective of this research is to investigate and evaluate how the mechanical properties of the cellular environment affect the AD-related microglial cell functions, in particular the oligomeric amyloid-β (Aβ) peptides uptake; for this purpose substrates with different stiffness are used to simulate AD and healthy brains and the amyloid-β uptake by microglial BV-2 cells is measured. The results demonstrate that the elasticity of the matrix influences the proliferation capabilities of the microglial cells, and also it has effects on the amyloid internalization by the immune cells of the central nervous system: a higher amyloid-β uptake is observed on softer substrate, that mimic the diseased brain tissue, compared to harder surface, that represents an healthy brain. An over-activation of microglial cells by Aβ could lead to an excessive neuroinflammation, extracellular deposition of Aβ into plaques, redundant production of cytotoxic products and, ultimately, to neuronal death; therefore, the study of the influence of different substrate stiffness on microglial cell functions could be a novel approach in the identification of possible therapeutic targets for the prevention of AD.