Transport of lipid vesicles via the cilia logistic network in the brain of mice

by Ann-Kathrin Günther
Doctoral thesis
Date of Examination:2018-09-21
Date of issue:2019-09-13
Advisor:Prof. Dr. Gregor Eichele
Referee:Prof. Dr. Gregor Eichele
Referee:Prof. Dr. Eberhard Bodenschatz
Persistent Address: http://dx.doi.org/10.53846/goediss-7642

 

 

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Abstract

English

The ventricular system of the mammalian brain consists of four interconnected cavities, which are lined by ciliated ependymal cells. Constant and coordinated movement of the cilia results in a directed flow of cerebrospinal fluid (CSF) along the ependymal walls. In the ventral part of the third ventricle (v3V) the cilia give rise to a complex network of flow that confines and connects regions. This so-called ciliary logistic network (CLN) may provide transport routes for CSF components (e.g. extracellular vesicles) and has the potential to guide and restrict the distribution of local secretions. It is unclear, how extracellular vesicles like exosomes are distributed throughout the ventricular system and whether the CLN mediates site-specific deliveries of exosomes. In this thesis, a characterization of exosome-like cargo transport along the CLN and potential target sites in the v3V of the mouse brain are presented. To investigate the transport and interaction of exosome-like cargo, fluorescently-labelled liposomes of defined composition and size were applied to the cilia-generated near wall flow via microinjections. The results of this work reveal that the transport of lipid vesicles within the v3V is determined by the cilia-generated flow. Liposomes are transported with high precision and interact with ependymal cilia in specific regions.
Keywords: ventral thrid ventricle; cilia-generated flow; liposomes; extracellular vesicles; ciliary logistic network; CSF transport
 
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