Investigation of Ca2plus homeostasis and behavioral changes in transgenic mice overexpressing key store-operated calcium entry proteins

• Autorzy: Maciag F. , Majewski L. , Boguszewski P.M. , Kuznicki J.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Store-operated calcium entry (SOCE) is the major Ca2+ influx pathway in non-excitable cells. However, recent studies suggest its important roles in neurons. In SOCE, the depletion of Ca2+ from the endoplasmic reticulum (ER) causes an influx of Ca2+ from the extracellular space to refill the intracellular Ca2+ stores. STIMs are Ca2+ ER sensors that mediate SOCE by interacting with the ion channels in the cell membrane – ORAIs. Using transgenic mice with neuronal overexpression of STIMs and/or ORAIs, we investigate their role in neural function. Recently, we showed electrophysiological changes in hippocampi from female mice overexpressing ORAI1. Earlier studies from our group revealed increased cytoplasmic Ca2+ levels in cultured neurons overexpressing both ORAI1 and STIM2. Currently, we are extending these studies with the use of double transgenic STIM2/ORAI1 mice. AIM(S): To investigate the role of SOCE proteins in neurons, and the effect of STIM2 and ORAI1 overexpression on Ca2+ homeostasis, synaptic functions, and behavior. METHOD(S): We use transgenic mice that overexpress STIM and/or ORAI proteins in brain neurons. For studying Ca2+ homeostasis, we stain hippocampal slices with Fura‑2 AM probe. To assess locomotor functions and cognitive abilities of these mice, behavioral tests are utilized. Synaptic transmission and plasticity phenomena are investigated by electrophysiological recordings from hippocampal slices. RESULTS: We have recently observed spontaneous seizure-like events in aged female mice overexpressing ORAI1. These observations correlated with changes in the response of hippocampal slices to pro-epileptic drugs. Currently, we are focusing our analyses on the double transgenic STIM2/ORAI1 mouse line. CONCLUSIONS: Our previous data support the view that SOCE proteins play an important role in neurons. Currently, we aim to elucidate the involvement of STIM2 and ORAI1 proteins in neural function. FINANCIAL SUPPORT: Maestro to JK from NCN (2011/02/A/NZ3/00144).

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2019
• Tom: 79
• Numer: Suppl.1
• Opis fizyczny: p.LXXXV

Twórcy

autor

Maciag F.

• Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland

autor

Majewski L.

• Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland

autor

Boguszewski P.M.

• Neurobiology Centre Laboratory of Molecular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Kuznicki J.

• Laboratory of Neurodegeneration, International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland