Redoxmodulation epileptischer Anfälle in einem Mausmodell für das Rett-Syndrom.

Redox modulation of epileptic seizures in a mouse model of Rett syndrome.

by Niklas Held
Doctoral thesis
Date of Examination:2024-10-23
Date of issue:2024-10-16
Advisor:Prof. Dr. Michael Müller
Referee:Prof. Dr. Michael Müller
Referee:Prof. Dr. Thomas A. Bayer
Referee:Prof. Dr. Margarete Schön
Persistent Address: http://dx.doi.org/10.53846/goediss-10796

 

 

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Abstract

English

The aim of the present dissertation was to investigate and evaluate the therapeutic benefit of an oral antioxidant therapy on the epilepsy symptoms associated with Rett syndrome. A shift in the cellular redox balance towards more oxidative conditions, as well as reduced serum levels of antioxidants, are observed changes in this complex neurological developmental disorder, suggesting that the restoration of the cellular redox balance may be a promising therapeutic approach. In addition to the improvements in various parameters previously described by the research group following antioxidant treatment, the impact on the complex symptom of seizure propensity in a mouse model of Rett syndrome was to be examined more closely. For this purpose, brain slices from both wild-type and Mecp2-/y mice, with and without antioxidant treatment, were electrophysiologically investigated by provoking seizure-like events with proconvulsant substances and recording them in the hippocampus and cortex regions. The detected discharges were analyzed regarding the parameters of discharge frequency, amplitude, and temporal onset to describe a potential anticonvulsant effect between the genotypically different groups. Both frequency and amplitude of the discharges showed trends towards improvement in terms of reduced seizure propensity in the antioxidant-treated knockout groups; however, due to a large standard deviation of the collected data, no statistical significance could be demonstrated. The analyzed onset times of the first hippocampal discharges as well as the cortical spreading depressions exhibited an ambivalent outcome, thus proving to be less effective descriptive parameters for seizure propensity in the investigated mouse model. In summary, it can be concluded that oral administration of an antioxidant cocktail did not demonstrate a significant effect on seizure propensity in the Rett mouse model. However, trends towards improvement in individual parameters were observed, supporting further investigation of therapeutic redox stabilization as a treatment approach for epilepsy in Rett syndrome. This work expands the limited existing research findings regarding the significance of redox imbalance for epilepsy symptoms in Rett syndrome. The insights into the limitations of the present study may be useful for future investigations on this topic. The neurobiology of epilepsy in Rett syndrome, which remains poorly understood to date, requires further in-depth studies, particularly considering the significant burden this often complex symptom places on Rett patients.
Keywords: methyl-CpG-binding protein 2; mecp2 knockout mouse model; antioxidant feed; rett syndrome
Schlagwörter: Rett-Syndrom; Epilepsie; Mecp2; Redox-Imbalance; Mecp2 knockout Mausmodell
 
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