Brain glial interface: Advance materials and devices targeting molecular and functional study of astrocytes

Borrachero Conejo, Ana Isabel (2019) Brain glial interface: Advance materials and devices targeting molecular and functional study of astrocytes, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Biologia cellulare e molecolare, 31 Ciclo. DOI 10.6092/unibo/amsdottorato/9009.
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Astrocytes are fundamental for the physiology of the central nervous system. Indeed, astrocytes dysfunction has been observed in many brain pathologies making them an attractive target for innovative therapeutical approaches. Proteins mediating calcium signaling are critically implicated in astrocytic function and dysfunction. However, state-of-the-art tools to study and modulate astroglial functions faced limited spatio-temporal sensitivity, cell selectivity and low throughput. While the use of materials and devices enabling photo- and electrical stimulation, have been shown to modulate neuronal activity, their potential to selectively alter astroglial behaviour have largely been neglected. To address this challenging issue, we use materials and devices to modulate and study astrocytes physiology in vitro. We present a device based on N, N’-ditridecylperylene-3,4,9,10-tetracarboxylic diimide (P13), that enables electrical stimulation of astrocytes by evoking increases in intracellular calcium concentrations in primary astrocytes. Pharmacological evidences show that the channels TRPV4 and TRPA1 are critically implicated in the observed effect. Moreover, we show that electrical stimulation promotes also cell swelling. We also explore the potential of graphene-based materials as neural interface by using graphene oxide functionalized with a phospholipid (GO-PL). We demonstrate that GO-PL allows an enhanced adhesion of astrocytes without promoting gliosis, that is not caused by modification of physicochemical properties. Finally, we investigate the effect of infrared neural stimulation (INS) on Ca2+-signaling in vitro and in a validated cell culture model of differentiated astrocytes demonstrating that INS represents a new label-free method to modulate astroglial Ca2+-signaling in vitro. Pharmacology and siRNA experiments, show that INS evoke extracellular Ca2+ influx, mediated by TRPV4 and TRPA1 channels, and Ca2+ release from intracellular stores. Notably, experiments on astrocytes from AQP4-KO-/- showed a delayed response. Collectively, we show the impact of novel technologies for understanding the mechanisms behind astrocytes function as well as the use of this technologies to target astrocyte functioning.

Tipologia del documento
Tesi di dottorato
Borrachero Conejo, Ana Isabel
Dottorato di ricerca
Settore disciplinare
Settore concorsuale
Parole chiave
Astrocytes, calcium signaling, biomaterials, electronic devices, photostimulation
Data di discussione
4 Aprile 2019

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