The effect of tetrahydrocarbozoles on the ER calcium release and SOCE in medium spiny neurons from transgenic YAC128 mice, a model of Huntington's disease

• Autorzy: Maciag F. , Czeredys M. , Kuznicki J.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Huntington’s disease (HD) is a genetic neurodegenerative disorder caused by an extended polyglutamine tail in the huntingtin (HTT) protein and manifesting itself by neurodegeneration of medium spiny neurons (MSN) in the striatum. An early event in the pathology of HD is deregulated Ca2+ homeostasis (Giacomello et al. 2013). One of the mechanisms that regulate Ca2+ homeostasis is store-operated Ca2+ entry (SOCE), which was shown to be enhanced in HD (Wu et al. 2011). However, the mechanism by which mutated HTT affects SOCE is still unknown and there is no effective treatment of HD. RESULTS: Therefore, we assessed the alterations of the Ca2+ signalosome in the striatum of transgenic YAC128 mice, a model of HD (Czeredys et al. 2013). In MSN isolated from these mice we detected an about 10% increase in the basal Ca2+ level. We found that the activity of SOCE was enhanced about 30%. Since the deregulation of Ca2+ homeostasis and signaling is considered to be the primary event in HD, the aim of this work was to investigate the effect of compounds called tetrahydrocarbazoles on the ER Ca2+ release induced by mGluR1/5 receptor agonist, DHPG (3,5-dihydroxyglycine), as well as their influence on SOCE in MSN from YAC128 mice. It was previously shown that tetrahydrocarbazoles stabilize the ER Ca2+ release induced by carbachole in HEK293 cells overexpressing mutated presenilin 1, a cellular Alzheimer’s disease model (Honarnejad et al. 2014). We have confirmed by immunostaining that in our in vitro model of HD, MSN culture from YAC128 mice, mGluR1/5 receptors are specifically expressed. The MSN cells were treated with chosen tetrahydrocarbazoles and Ca2+ was imaged with Fura-2 AM. CONCLUSIONS: Our preliminary data suggest that some tested compounds have a stabilizing effect on Ca2+ level in HD cellular model. Tetrahydrocarbazoles could be potentially used as drugs stabilizing the disturbed Ca2+ homeostasis in Huntington’s disease.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S41-S42

Twórcy

autor

Maciag F.

• Warsaw University of Technology, Warsaw, Poland
• International Institute of Molecular and Cell Biology, Warsaw, Poland

autor

Czeredys M.

• International Institute of Molecular and Cell Biology, Warsaw, Poland

autor

Kuznicki J.

• International Institute of Molecular and Cell Biology, Warsaw, Poland