Brain Inflammation and Adult Hippocampal Neurogenesis in Epilepsy
Författare
Summary, in English
Given the importance of inflammation in epilepsy, the role of a specific immune signaling mediated by the chemokine fractalkine and CX3CR1 was investigated with an objective to modulate the seizure-induced pathology (Paper 3). Intracerebroventricular infusion of anti-CX3CR1 antibody immediately following SE for one week diminished microglial cell activation, neuronal degeneration, and neuroblast production. These findings open up the possibility that fractalkine-CX3CR1 pathway may have anti-epileptogenic effects, which would be an interesting aspect to pursue in future studies. We also demonstrate the direct structural interactions between newly formed hippocampal neurons and microglia during synaptogenesis in a physiological and seizure-induced pathological environment using two-photon and confocal microscopy (Paper 4). We show that ramified microglia change their regional preferences with respect to their interactions with the newborn neurons following SE. Relatively more interactions were observed with the proximal dendrites known to receive primarily inhibitory synaptic inputs. Finally, the last study proposes a panel of molecular markers regulating the brain inflammation and the E/I balance in synapsin2 knockout mouse model of epileptogenesis, which could be further developed as potential biomarkers (Paper 5).
In conclusion, this thesis describes the role of brain inflammation in regulating synaptic integration of newborn neurons. Our results also suggest that blocking CX3CR1 after seizures could be a promising therapeutic approach. Furthermore, our findings concerning the molecular changes related to brain inflammation and E/I balance in a genetic mouse model of epileptogenesis could aid the development of biomarkers in future.
Avdelning/ar
Publiceringsår
2015
Språk
Engelska
Publikation/Tidskrift/Serie
Lund University Faculty of Medicine Doctoral Dissertation Series
Volym
2015:60
Dokumenttyp
Doktorsavhandling
Förlag
Neurology, Lund
Ämne
- Neurology
Nyckelord
- Epilepsy
- Inflammation
- Neurogenesis
- Hippocampus
- Microglia
- Adhesion molecules
- Scaffolding proteins
Status
Published
Handledare
ISBN/ISSN/Övrigt
- ISSN: 1652-8220
- ISBN: 978-91-7619-139-2
Försvarsdatum
18 maj 2015
Försvarstid
13:00
Försvarsplats
Segerfalksalen, BMC A10, Sölvegatan 17, Lund.
Opponent
- William P. Gray (Prof.)