Translocator protein expression in an animal model of temporal lobe epilepsy: picturing a Janus face?

Epilepsy is a devastating disorder affecting 50 million people worldwide characterised by recurrent seizures and serious psychiatric comorbidities such as anxiety and depression. This research proposal will investigate a novel hypothesis connecting brain inflammation and neurosteriod alterations as protagonists during the development of epilepsy and its comorbidities a process termed epileptogenesis. These former pathways are shown to have bimodal effects on seizure susceptibility, but up till now have only been investigated independently. Our hypothesis of coupling these pathways is supported by the observation that i) the translocator protein (TSPO) a marker of brain inflammation is highly upregulated in epilepsy and ii) the main function of TSPO is cholesterol import, the rate-limiting step in steroidogenesis. Firstly, we will for the first time investigate the brain region and cell specific distribution pattern of TSPO during epileptogenesis and established epilepsy in two rat models of acquired epilepsy. Secondly, pharmacological agents will be used to interfere with TSPO and brain inflammation to investigate a causal relationship between TSPO and epileptogenesis by means of translational techniques namely in vivo TSPO PET imaging, behavioural tests and video-EEG monitoring in a rat model of temporal lobe epilepsy. This innovative project will increase our understanding of the ambiguous complexities related to brain inflammation- and neurosteriod-induced effects on brain excitability potentially revealing an interrelated action. If the proposed hypothesis holds true, this may influence our current thinking regarding the role of brain inflammation in epilepsy and psychiatric conditions.

Keywords:EXPERIMENTAL STUDY, TRANSLOCATOR PROTEIN, EPILEPSY MODEL, NEURO-IMAGING

Disciplines:Medical imaging and therapy, Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing