uPAR-interactome and post-traumatic epileptogenesis

 

 

 

Our molecular profiling study of epileptogenesis after status epilepticus (SE) showed that the most upregulated gene was urokinase-type plasminogen activator (uPA). Data on uPA from the cancer field demonstrates the role of uPAR-interactome [uPAR, its extracellular ligands such as uPA and and sushi-repeat protein X-linked SRPX2, and its membrane receptor partners] in cancer cell adhesion, proliferation, differentiation and migration; matrix degradation; invasion and clearance of inflammatory cells; apoptosis, and tumor angiogenesis. Many of these processes occur in the brain during acquired epileptogenesis. Moreover, uPAR-/- mice have epilepsy that is associated with abnormal migration of GABAergic interneurons in the frontal cortex and the hippocampus and patients with Rolandic epilepsy with speech impairment or bilateral perisylvian polymicrogyria have a mutation in a gene encoding SRPX2 protein (Sushi-Repeat Protein, X-linked) that is a ligand of uPAR. Recently we have found that SRPX2 is expressed in the perilesional cortex after TBI. IN this project, we aim: (1) To identify regional and cellular location of SRPX2 expression during post-TBI epileptogenesis, (2) To identify signaling mechanisms by which SRPX2 regulates post-TBI axonal plasticity, (3) To measure the circulating levels of SRPX2 during epileptogenesis to correlate whether plasma levels correlate with expression in brain tissue, and assess whether plasma SRPX2 values serve as biomarker for its actions in the brain on plasticity, (4) To suppress the expression of SRPX2 in the hypothalamus with siRNA and assess its effect on acute neurodegeneration and axonal plasticity, (5) To assess whether the treatment effect on synaptic plasticity can be monitored with in vivo MRI imaging and using multielectrode arrays in brain slices.

 

 

 

Supervisors: Pr. Asla Pitkänen

 

 

For more information about the post and to submit your application, please go to http://www.uef.fi/en/uef/en-open-positions and choose Early Stage Researcher H2020-MSCA-ITN

 

For details about the post, please contact: Prof. Asla Pitkänen