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Altering the fate of newborn cells in the hippocampus after status epilepticus

Torres Di Bello, Daniela (2021) MOBN02 20202
Degree Projects in Molecular Biology
Popular Abstract
Altering the fate of newborn cells in the hippocampus after status epilepticus

Epilepsy is a common neurological disorder that is estimated to affect approximately 50 million people around the world according to the World Health Organization. This disorder is characterized by an increase in the predisposition to generate seizures, which are periods of hyperexcitable neuronal signaling. The treatment for this condition includes various anti-seizure drugs and in some cases surgery. However, available treatment strategies are not sufficient to help all patients to become seizure-free, and 1 in 3 patients present resistance to drug therapy, according to the International League against epilepsy (ILAE). Due to these reasons, a new treatment... (More)
Altering the fate of newborn cells in the hippocampus after status epilepticus

Epilepsy is a common neurological disorder that is estimated to affect approximately 50 million people around the world according to the World Health Organization. This disorder is characterized by an increase in the predisposition to generate seizures, which are periods of hyperexcitable neuronal signaling. The treatment for this condition includes various anti-seizure drugs and in some cases surgery. However, available treatment strategies are not sufficient to help all patients to become seizure-free, and 1 in 3 patients present resistance to drug therapy, according to the International League against epilepsy (ILAE). Due to these reasons, a new treatment is highly warranted. Faced with these treatment-related problems, gene therapy has been proposed to target aberrant neurogenesis which is one of the main hallmarks of epilepsy. This could provide researchers with a better understanding of the disease and might result in better treatment strategies. To add more knowledge of neurogenesis in epilepsy and to complement a study carried out previously in the Epilepsy Centre, in this project we tried to redirect the differentiation of newborn neurons utilizing a viral vector targeting neurogenesis in the epileptic mouse hippocampus.

The aim of this project was to, firs induce status epilepticus (SE) in the C57BL/6JRj mouse model of temporal lobe epilepsy. This was achieved by using a systemic low repeated dose (5mg/kg) of kainic acid. The characterization of the seizures was obtained by classifying the behavioral seizures using the modified Racine scale. After one week, we injected two viral vectors, one containing Ascl1-GFP to re-direct the neurogenesis and another containing RFP as a control. Four weeks after the viral injections we performed immunohistochemistry of the mouse brain tissue in order to observe the transfected cells. We found that status epilepticus can significantly increase the number of these newly generated cells and provokes a context dependent effect in the localization of the Ascl1- GFP transfected cells. However, the Ascl1-GFP transfected cells appears to be an heterogenous population even under normal physiological conditions. As consequence, SE has a substantial effect on the re-direction process meaning that additional components should be included in the viral vector creation process to potentially resolve this problem. Future studies would require a detailed analysis of transfected cells' cellular fate in a chronic TLE animal model with a higher translational value.

Master’s Degree project in Molecular Biology, General, 45 credits 2021
Department of biology, Lund University

Advisor: Esbjörn Melin
Experimental Epilepsy Center, Department of clinical sciences, Lund Universit (Less)
Please use this url to cite or link to this publication:
author
Torres Di Bello, Daniela
supervisor
organization
course
MOBN02 20202
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
9042819
date added to LUP
2021-04-06 12:45:35
date last changed
2021-04-06 12:45:35
@misc{9042819,
  author       = {{Torres Di Bello, Daniela}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Altering the fate of newborn cells in the hippocampus after status epilepticus}},
  year         = {{2021}},
}