Forsøksdyr: Role of astrocyte signaling in brain waste removal

Godkjenningsdato 02.07.2020

Godkjenningsperiode 02.07.2020-02.07.2023

The brain does not have a conventional lymphatic system for draining waste products. The precise mechanisms that govern the brain CSF circulation and waste clearance are unknown. We aim to map the molecular mechanisms involved in brain waste clearance. In particular, in this project we want to determine the role of Ca2+ transients in astrocytes in regulation of tracers flow into and out of brain. IP3R2 KO has severely reduced Ca2+ transients in astrocytes. We test the hypothesis IP3R2 KO mice has altered CSF flow and clearance of waste products out of the brain.

We plan on doing this by injecting different tracers into the CSF and brain parenchyma of IP3R2 KO/WT mice in awake and sleeping mice and evaluate tracer clearance. We will use radioactive tracers to quantify the tracer clearance rate, and fluorescent tracers to visualize the spatial distribution of the tracer and its exit pathway.

The project will provide increased information of brain waste drainage mechanisms. Such insight is important to understand diseases such as Alzheimer's disease where waste products accumulate, inducing cell death and cognitive defecits .
The project is a continuation of previous projects 11942 and 11938.