Position Host institution PhD enrolment Start date Duration
ESR8 P6-UKB Y (at UKB) early 2017 36 months


Project Title:

Mechanisms underlying uncoupling of astrocytes in the epileptic brain


Objectives:

In human temporal lobe epilepsy (TLE), patients with hippocampal sclerosis (HS) show lack of gap junction coupling among astrocytes. In a TLE mouse model, unilateral intracortical kainate injection, morphological and functional changes reproduce those seen in chronic human HS. Importantly, uncoupling of astrocytes occurs already within 4 h after onset of status epilepticus (SE), thus preceding changes in neurons and generation of recurrent seizures (Bedner et al., 2015, Brain 138:1208). However, the mechanisms underlying SE-induced uncoupling are unclear.

 

Methodology:

We will use reporter mice for Cx43 expression (Cx43kiECFP), immunodetection with antibodies recognizing distinct Cx43 phosphorylation sites and mass spectrometry to find out whether reduced expression or post-translational modification of Cx43 account for decreased coupling in TLE. Preliminary data indicate a role for pro-inflammatory cytokines in SE-induced gap junction blockade. Using mice lacking the corresponding receptors (TLR4 KO, IL-R1 KO, TNF-R1 KO, IL-R1/TNF-R1 dKO) or applying receptor antagonists (LPS-RS, IL-1ra, XPro1595) the underlying mechanisms will be explored.

 

Christian SteinhäuserCSteinhaeuser

University of Bonn

This email address is being protected from spambots. You need JavaScript enabled to view it.
https://www.izn.uni-bonn.de