Spatio-temporal properties of neurotrophin signalling in tauopathy

Abstract

Neuronal cells form a highly organised neuronal network that allows us to function in everyday life. In order to maintain a healthy network, neuronal brain cells synthesise and secrete growth factors. Brain-derived neurotrophic growth factor (BDNF) is one of the growth factors widely expressed in the brain. Its role is to induce cell growth and strengthen connections between neuronal cells.

A significant decrease in the amount of BDNF has been detected in the brains of individuals who have suffered from neurodegenerative diseases such as Alzheimer’s disease, compared to healthy brains. Upregulating BDNF could be a potential therapeutic strategy to strengthen the connections of vulnerable neurons before the onset of neuronal death.

My PhD project looks to investigate to which degree BDNF-TrkB signalling is intact, both locally and over long-distances in neuronal brain cells that express a disease relevant mutation and whether these signals can support the vulnerable neuronal brain cells. In order to investigate this, I expressed a tauopathy related mutation (TauP301L) in embryonic mouse neuronal brain cells. I have observed disruption in BDNF transport and a significant change in the expression of its receptor, TrkB, at distal axons on TauP301L-expressing neurons. To assess BDNF signal relay, I have set-up a microfluidic platform that allows us to investigate both local and long-distance intracellular signalling of BDNF. I have seen a disruption in BDNF signalling in TauP301L-expressing neurons. This research gives us insight into whether growth factors are feasible for therapeutic strategies.

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Identifiers

ORCID for Katrin Deinhardt: orcid.org/0000-0002-6473-5298

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