Modulation hippokampaler neuronaler Apoptose und Neurogenese durch Fas apoptotic inhibitory molecule 2 (Faim2) im Rahmen der experimentellen Streptokokkenmeningitis

Harms, Kristian

dc.contributor.advisor	Schulz, Jörg B. Prof. Dr.
dc.contributor.author	Harms, Kristian
dc.date.accessioned	2014-01-06T12:35:49Z
dc.date.available	2014-01-14T23:50:04Z
dc.date.issued	2014-01-06
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-0022-60AA-7
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-4276
dc.language.iso	deu	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.ddc	610	de
dc.title	Modulation hippokampaler neuronaler Apoptose und Neurogenese durch Fas apoptotic inhibitory molecule 2 (Faim2) im Rahmen der experimentellen Streptokokkenmeningitis	de
dc.type	doctoralThesis	de
dc.title.translated	Modulation of hippocampal neuronal apoptosis and neurogenesis by Fas apoptotic inhibitory molecule 2 (Faim2) in the course of experimental streptococcal meningitis	de
dc.contributor.referee	Schulz, Jörg B. Prof. Dr.
dc.date.examination	2014-01-07
dc.description.abstracteng	Fas apoptotic inhibitory molecule 2 (Faim2) is a neuron-specific membrane protein and a member of the evolutionary conserved lifeguard (LFG) apoptosis regulatory gene family, acting as a proximal inhibitor of the Fas-FasL signaling pathway. Applying a Faim2-deficient null mutant mouse line, its involvement in neurological diseases with neuroprotective anti-apoptotic effects has recently been demonstrated in an in vivo model of focal cerebral ischemia. In this study, immediate and sustaining effects of Faim2 were investigated in a well-established mouse model of Streptococcus pneumoniae type 3 (SP3) meningitis. Leaving neuroinflammation, clinical course and survival unaltered, lack of Faim2 resulted in an increase of caspase-associated apoptotic cell death of hippocampal neurons during acute bacterial meningitis induced by subarachnoid infection with SP3 in mice. In Faim2 wild-type mice, neuroinflammation induced a divergent regulation of hippocampal Fas and Faim2 expression, revealing an increase of Fas and a decrease of Faim2 during acute bacterial meningitis. However, when mice were rescued by antibiotic treatment with ceftriaxone, Faim2-deficiency led to increased hippocampal neurogenesis several weeks after infection. As a sign for functional significance, this was associated with improved performance of Faim2-deficient mice compared to wild-type littermates in the Morris water maze, a paradigm for hippocampal spatial learning and memory, and increased exploratory behaviour. Additionally, clinical impairment and mortality was reduced and motor coordination improved related to Faim2-deficiency in ceftriaxone-treated cohorts. In summary, Faim2 influenced both neuroprotective and regenerative processes in a time-dependent manner in a mouse model of pneumococcal meningitis. Hence, modulation of Faim2 may offer new therapeutic approaches for improving outcome after bacterial meningitis.	de
dc.contributor.coReferee	Spreer, Annette PD Dr.
dc.subject.ger	Fas apoptotic inhibitory molecule 2 (Faim2)	de
dc.subject.ger	lifeguard (LFG)	de
dc.subject.ger	Fas/CD95	de
dc.subject.ger	Streptococcus pneumoniae	de
dc.subject.ger	bakterielle Meningitis	de
dc.subject.ger	Neuroinflammation	de
dc.subject.ger	hippokampale Apoptose und Neurogenese	de
dc.subject.ger	räumliches Lernen und Gedächtnis	de
dc.subject.ger	Morris-Wasserlabyrinth	de
dc.subject.ger	Neuroprotektion	de
dc.subject.ger	Neuroregeneration	de
dc.subject.eng	Fas apoptotic inhibitory molecule 2 (Faim2)	de
dc.subject.eng	lifeguard (LFG)	de
dc.subject.eng	Fas/CD95	de
dc.subject.eng	Streptococcus pneumoniae	de
dc.subject.eng	bacterial meningitis	de
dc.subject.eng	neuroinflammation	de
dc.subject.eng	hippocampal apoptosis and neurogenesis	de
dc.subject.eng	spatial learning and memory	de
dc.subject.eng	Morris water maze	de
dc.subject.eng	neuroprotection	de
dc.subject.eng	neuroregeneration	de
dc.identifier.urn	urn:nbn:de:gbv:7-11858/00-1735-0000-0022-60AA-7-9
dc.affiliation.institute	Medizinische Fakultät	de
dc.subject.gokfull	Medizin (PPN619874732)	de
dc.description.embargoed	2014-01-14
dc.identifier.ppn	775646970

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Human- und Zahnmedizin [2872]

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