Epileptic seizures and oxidative stress in a mouse model over-expressing spermine oxidase.
Alessia LeonettiGiulia BaroliEmiliano FratiniStefano PietropaoliManuela MarcoliPaolo MariottiniManuela CervelliPublished in: Amino acids (2019)
Several studies have demonstrated high polyamine levels in brain diseases such as epilepsy. Epilepsy is the fourth most common neurological disorder and affects people of all ages. Excitotoxic stress has been associated with epilepsy and it is considered one of the main causes of neuronal degeneration and death. The transgenic mouse line Dach-SMOX, with CD1 background, specifically overexpressing spermine oxidase in brain cortex, has been proven to be highly susceptible to epileptic seizures and excitotoxic stress induced by kainic acid. In this study, we analysed the effect of spermine oxidase over-expression in a different epileptic model, pentylenetetrazole. Behavioural evaluations of transgenic mice compared to controls showed a higher susceptibility towards pentylentetrazole. High-performance liquid chromatography analysis of transgenic brain from treated mice revealed altered polyamine content. Immunoistochemical analysis indicated a rise of 8-oxo-7,8-dihydro-2'-deoxyguanosine, demonstrating an increase in oxidative damage, and an augmentation of system xc- as a defence mechanism. This cascade of events can be initially linked to an increase in protein kinase C alpha, as shown by Western blot. This research points out the role of spermine oxidase, as a hydrogen peroxide producer, in the oxidative stress during epilepsy. Moreover, Dach-SMOX susceptibility demonstrated by two different epileptic models strongly indicates this transgenic mouse line as a potential animal model to study epilepsy.
Keyphrases
- hydrogen peroxide
- oxidative stress
- temporal lobe epilepsy
- high performance liquid chromatography
- resting state
- white matter
- mouse model
- cerebral ischemia
- functional connectivity
- protein kinase
- tandem mass spectrometry
- type diabetes
- ischemia reperfusion injury
- adipose tissue
- mass spectrometry
- single cell
- metabolic syndrome
- diabetic rats
- ms ms
- induced apoptosis
- insulin resistance
- binding protein
- high resolution
- simultaneous determination
- long non coding rna
- heat shock
- signaling pathway
- data analysis
- heat shock protein
- newly diagnosed