Investigating the Impact of Hypoxia on Gene Expression in the Brain of a Mouse Model for the Rett Syndrome

von Susann Özel
Dissertation
Datum der mündl. Prüfung:2015-02-02
Erschienen:2015-01-27
Betreuer:PD Dr. Dr. Till Manzke
Gutachter:PD Dr. Dr. Till Manzke
Gutachter:PD Dr. Marco Henneke
Zum Verlinken/Zitieren: http://dx.doi.org/10.53846/goediss-4891

 

 

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Englisch

The Rett syndrome (RTT) is a neurodevelopmental disorder that is associated with mutations of the MECP2 gene, which encodes for the transcriptional regulator methyl CpG binding protein 2 (MeCP2). This study clarifies whether respiratory irregularities of MeCP2 deficient mice (Mecp2-/y) as a model for RTT evoke systemic hypoxia throughout the brain causing breathing aberrations and thus one of the syndrome’s most life threatening features. So far literature on RTT induced hypoxia has demonstrated an elevated hypoxia gene expression in brains of older Mecp2-/y mice. However, the limited number of studies available concentrated on HIF-1α levels only. Other hypoxia related genes have so far been ignored. To fill this gap in the literature, five brain areas (cerebellum, cortex, inferior olive, hypothalamus, and ventral respiratory column) were analyzed in Mecp2-/y males at postnatal day (P) 40 for hypoxia-associated gene deviations using the qRT-PCR and western blot technique. This study found that respiratory disorders neither provoke an induction of hypoxia genes nor increased HIF-1α protein levels. However, metabolism-affecting thyroliberin gene (Trh) expression was strongly increased. As a consequence, Trh up-regulation possibly circumvents hypoxia of Mecp2-/y mice and might explain the typical emaciated phenotype of Mecp2-/y mice. This is the first study indicating that in Mecp2-/y mice TRH might act as a potent counter-regulator that induces adaption mechanisms within the respiratory network. 
Keywords: Rett syndrome; hypoxia; brain; gene expression; thyroliberin
 
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