The contribution of P2X7R and microglial activation in the neurological deficits of temporal lobe epilepsy

Research Opportunity
PhD, Masters by Research, Honours, Master of Biomedical Science
Project Status
Future
Department
Medicine and Radiology
Location
Royal Melbourne Hospital
Supervisor Email Number Webpage
Dr Mastura Monif mmonif@unimelb.edu.au Personal web page
Professor Terry O'Brien obrientj@unimelb.edu.au Personal web page

Project Details

Epilepsy is a neurological condition characterized by recurrent unprovoked seizures that affects approximately 1% of the global population. In temporal lobe epilepsy (TLE) the seizures originate from the medial or lateral temporal lobe. TLE is frequently associated with hippocampal sclerosis (HS) with significant neurodegeneration, as well as activation of microglia in various regions of the hippocampus. HS is observed in approximately 70% of surgical specimens from patients undergoing surgery for drug-resistant seizures. Previous studies in animals have shown that a specific receptor, P2X7R, is over-expressed in acute and chronic phases of TLE in glial cells of the hippocampus, suggesting an involvement of this receptor in disease pathogenesis. Similarly in the region of HS there is enhanced activation of microglial cell.

For the first series of studies we will be characterizing the presence of P2X7R and activated microglia in temporal lobectomy specimens from epilepsy patients undergoing surgery. Temporal lobectomy samples with HS will be compared to non-HS. Presurgical MRI data will be used to confirm HS. Some of the questions that we will be addressing are: Is P2X7R expression increased in HS versus non-HS TLE?

Techniques: immunohistochemistry confirmed by mRNA levels (real time PCR). Does the level of P2X7R expression in the hippocampus correlate with the degree of neuronal loss? Is microglial activation increased in HS versus non-HS TLE?

Techniques: immunohistochemistry on primary human cultures or organotypic brain slices. Does the level of microglial activation in the hippocampus (from temporal lobectomy patients) correlate with the degree of neuronal loss? Understanding the role of P2X7R and microglial activation in temporal lobe epilepsy would assist in the development of more targeted therapies to combat this devastating and debilitating condition.

Research Opportunities

This research project is available to PhD, Masters by Research, Honours, Master of Biomedical Science students to join as part of their thesis.
Please contact the supervisor to discuss your options.



Faculty Research Themes

Neuroscience

School Research Themes

Neuroscience & Psychiatry



Key Contact

For further information about this research, please contact a supervisor.

Department

Medicine and Radiology

Research Node

Royal Melbourne Hospital