ESR 6 - Eleonora Lugarà

UCL, London, UK

Eleonora 1

I did my Bachelor's degree and Master's degree in Medical Pharmaceutical Biotechnology, specialising in Neuroscience, at the University of Genova, Italy. During these years, I have also been involved in several research projects. Firstly, I learnt during my Bachelor's degree about patch clamp and optogenetics techniques on an in vitro epilepsy model at the Italian Institute of Technology (Genova, Italy). Hereafter, I took part in the Erasmus programme where I practiced immunohistochemistry and behavioural test at the Royal College of Surgeons (Ireland). Lastly, I received a fellowship to work at the IINS Institute of Bordeaux (France) on Synapsin-I KO model using the double patch clamp technique.

 At present time, I am a PhD student at University College London (UK) and my project is about understanding the role and interactions of LGI1 protein in acute and chronic models of epilepsy. 


Role of LGI1 in the expression and treatment of acquired epilepsy


Hosted at UCL


Background

LGI1 is an excreted protein that is necessary for the function and trafficking of presynaptic Kv1.1 and also for the trafficking of AMPA receptors. Mutations in the gene encoding LGI1 result in epilepsy in humans and autoantibodies to LGI1 cause seizures and limbic encephalitis in humans. We have recently found LGI1 to be reduced in acquired epilepsy in animals and this is associated with a loss of function of presynaptic potassium channels. Here we will determine if this is sufficient to cause epilepsy and whether redressing this is an effective antiepileptogenic strategy.

Objectives

  • To determine if reduction of LGI1 expression or prevention of interaction with ADAM22/23 affects presynaptic and post-synaptic excitability 
  • To determine if reduction of LGI1 interactions with ADAM22/23 are sufficient to result in epileptogenesis 
  • To determine if increasing LGI1 expression can prevent the development of acquired epilepsy.

Approach

Modulators developed by Iproteos and DZNE to disrupt LGI1 interaction with presynaptic ADAM23-Kv1.1 complex or postsynaptic ADAM22-PSD95 complex and/or shRNA to LGI1 will be applied to hippocampal neuronal cultures and the effects on firing properties and presynaptic neurotransmitter release will be determined. The most effective of these approaches will then be applied in vivo to the hippocampus of post-status epilepticus rodents. Patch clamp recordings from pyramidal cells and interneurons will made in acute ex vivo slices (from post-status epilepticus rodents) to determine the effects of treatments on presynaptic release probability and amplitude of postsynaptic responses elicited by mossy fiber stimulation. If this has an effect, then we will implant wireless transmitters and use extradural screws to monitor EEG continuously for up to 3 months in post-status epilepticus rodents. If no seizures are recorded, we will test seizure threshold using kainic acid in the same rats. We will also assess cognition using alternating T-maze. Lastly we will try to prevent epileptogenesis in acquired epilepsy (post-status epilepticus) by using either LGI or by overexpressing LGI1 using a viral vector or by application of LGI1 mimetics in post-status epilepticus rodents.

Collaborations

DZNE, Iproteos, AMU and Vect-Horus will be involved in generating relevant reagents.

Current Activity

After successfully submitted her PhD thesis on "Acute effects of LGI1 on network excitability", Eleonora is working at UCL in the same laboratory, as Post-Doc Researcher.

Page last modified on 21 may 19 11:16