Roles of different glial populations in neuronal maturation: implications in Rett Syndrome and Alzheimer's disease
Year: 2015
Type: dissertation
Abstract: It is well established that in healthy brain, the interplay between neurons and glia play a very important role in the maintenance of a correct physiological activity.Recent studies have shown the existence of an active involvement of glia in both the formation and function of the synapse (Araque et al. 1999;Parpura et al. 2012).These findings have led to reconsider the role of glia also in the case of pathological situations.Indeed, beyond its fundamental implication in healthy brain, glia has been found to play a critical role in several neurological disorders.It is now clear (Nguyen at al. 2012, Maezawa and Jin, 2010) that glial cells are involved not only in neurodegenerative diseases such as Alzheimer's disease (Angelova PR at al. 2014), but also in diseases characterized by intellectual disability.In this regard, recent evidence has shown the involvement of glial cells in Rett Syndrome (Ballas et al., 2009, Maezawa et al., 2009, Derecki et al., 2012Okabe 2012).The purpose of my thesis is to investigate the role of different populations of astrocytes in the development and survival of neurons using in vitro models of both neurodegenerative and neurodevelopmental disorders.To this aim, in the first part of my project I participated in the setting up of a microfluidic system, an experimental model aim at studying the interconnections between different brain cells, focusing my attention on the contribution of glial cells derived from different brain areas in these pathological states.Secondly, through the use of the microfluidic system, we have shown that astrocytes derived from distinct brain areas have different effects on neurons if exposed to several harmful stimuli.Specifically I have evaluated both the development and viability of hippocampal neurons co-cultured with either cortical or hippocampal astrocytes in a neuroinflammatory context represented by the stimulation of beta amyloid peptide (Aß) together with several proinflammatory cytokines.Taking advantage of the microfluidic system, we showed that hippocampal and cortical astrocytes exposed to these stimuli were able to significantly increase neuronal cell death.Interestingly, hippocampal astrocytes induced an elevated neuronal cell death if compared to cortical astrocytes.(
Author: R Mastrangelo
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W217372584