Modulation der Hypoxie-Empfindlichkeit medullärer Netzwerke in einem Maus-Modell des Rett-Syndroms

Modulation of hypoxia-susceptibility of medullary networks in a mouse-modell of Rett-syndrome

von Jasper Lukas Zimmermann
Dissertation
Datum der mündl. Prüfung:2012-02-14
Erschienen:2012-09-14
Betreuer:Prof. Dr. Michael Müller
Gutachter:Prof. Dr. Michael Müller
Gutachter:Prof. Dr. Peter Huppke
Zum Verlinken/Zitieren: http://dx.doi.org/10.53846/goediss-1610

 

 

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For this thesis I investigated if elicitation of hypoxia-induced spreading depression-like depolarizations (HSDs) in the brain stem of mice is possible. Furthermore I screened for differences in hypoxia susceptibility between Mecp2-/y- and wildtype-mice and whether hypoxia susceptibility could be influenced by 5-HT1A-receptor agonist 8-OH-DPAT. In addition I investigated the direct influence of HSDs on breathing-associated medullary rhythmic activity. Results show that HSDs can consistently be elicitated in brain stem of juvenile (p10-15) mice. Furthermore I detected an enhanced hypoxia susceptibility in Mecp2-/y-mice a mouse model for Rett syndrome. To investigate the influence of HSDs on medullary respiratory rhythm genesis I adapted the preparation of rhythmically active brain stem slices to interface chamber conditions. This allowed analysis of rhythmic brain stem activity at almost physiological conditions. Analysis of rhythmically active slices showed a complete reversible blockage of rhythmic activity upon occurrence of a HSDs. Combined with the results regarding an enhanced hypoxia susceptibility of these brainstem areas in Mecp2-/y-mice this might be a possible account for the often letal apneas in Mecp2-/y-mice as well as human Rett patients. Furthermore my results support the thesis that HSDs in brainstem might be a possible explanation for sudden infant death syndrome. By adding 50
Keywords: brain stem; Rett syndrome; Mecp2; hypoxia; sudden infant death syndrome; serotonine
Schlagwörter: Hirnstamm; Rett-Syndrom; Mecp2; Hypoxie; SIDS; plötzlicher Kindstod; Serotonin
 
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