@mastersthesis{10902/35592,
year = {2024},
month = {6},
url = {https://hdl.handle.net/10902/35592},
abstract = {Adult hippocampal neurogenesis, even though it has been controversial for a very long time,
persists in the brain of most mammal species during postnatal and adult life. Under physiologic
conditions, neurogenesis is an extremely regulated multi-step process where Neural Stem Cells
(NSCs) get activated continuously but with low frequency, and then divide giving rise to
amplifying neural progenitors (ANPs) which proliferate for a few days and then die by apoptosis,
being removed by microglia; or continue their neurogenic pathway, maturing into post-mitotic
neuroblasts that differentiate into new neurons. Any possible alteration, such as neuronal
hyperexcitation, can trickle down the neurogenic cascade. Neurogenic alterations have been
reported as a hallmark in several neurodegenerative diseases as epilepsy. Epileptic symptoms are
widely range, from convulsive to non-convulsive seizures, possible granule cell dispersion (GCD)
or astrogliosis. Neuronal activity levels may vary between patients. Here, by KA-induced epilepsy
murine models, we hypothesized that different levels of neuronal activity will trigger differential
response on NSCs. In order to answer this question our current efforts are now focused on
establishing mice models replicating the human natural course of hyperexcitation conditions by
standardizing a reliable model of epileptiform activity (EA) and mesial temporal lobe epilepsy
(MTLE) with mild sclerosis to investigate its effects on a hippocampal neurogenic niche.
We explored the divergent impacts of increased neuronal hyperexcitation induced by
intrahippocampal kainic acid (KA) injections (0.74 mM and 2.22 mM) in 3-month-old mice,
modelling Epileptiform Activity (LKA or EA) and Mesial Temporal Lobe Epilepsy (MTLE).
As expected, different KA doses cause distinct cellular response in the neurogenesis niche in DG.
Moreover, the morphologic changes that NSCs suffer when exposed to KA are caused by
enhanced neuronal activity thus the higher KA dose, the higher cell complexity and the larger
morphologic changes.},
title = {Functional and morphological characterization of neural stem cells in murine models of neuronal hyperexcitation},
author = {Varona de la Hera, Diego},
}