Neurogenesis in epilepsy- protective or disruptive?
- Research Opportunity
- Masters by Research, Honours
- Project Status
- Medicine and Radiology
- Royal Melbourne Hospital
|Dr. Idrish Aliemail@example.com|
|Dr. Chris French|
New neurons are generated continuously in the hippocampus throughout the lifetime of mammalian brain. They may contribute to cognitive functions, but have also been linked to pathophysiology of neurological disorders such as epilepsy and depression. In animal models of temporal lobe epilepsy, one of the most common forms of epilepsy, an acute transient increase in neural proliferation is evident. Depending on the precipitating injury that precedes epilepsy development, these neurons may migrate abnormally to the hilar region of the dentate gyrus and further contribute to the pathophysiology of epilepsy. Whereas, neurons that integrate within the hippocampal granule cell layer (GCL) may have protective effects as they are reported to receive reduced excitatory and enhanced inhibitory afferent inputs when compared to the new neurons from control animals. However, the exact role of seizure-induced neurogenesis in disease pathology is constantly debated.
Furthermore, approaches to ablate neurogenesis before and after an epileptogenic insult has provided mixed outcomes with regards to epilepsy development. In the current study we aim to investigate the physiological role of these newly formed neurons in epileptic pathological environment at various cross-sectional time-points during epilepsy development. Furthermore, we aim to investigate if structural/functional integration of new-born neurons is affected by the environment in which they are born (before or after epileptogenic insult) and the phase of epileptogenesis when their activity is measured. Adult new-born neurons will be labeled with retroviral-vector carrying a GCaMP6 gene before and immediately after the induction of status epilepticus in two different rat cohorts to enable calcium fluorophore imaging from those cells.
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