Behavioral and electrophysiological changes in female mice overexpressing ORAI1 in neurons

Maciąg, Filip; Majewski, Łukasz; Boguszewski, Paweł M.; Gupta, Rishikesh Kumar; Wasilewska, Iga; Wojtaś, Bartosz; Kuźnicki, Jacek

doi:10.1016/j.bbamcr.2019.01.007

Cited by 13 publications

(16 citation statements)

References 88 publications

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“…Moreover, male mice of STIM2/ORAI1 manifested altered recognition of the novel object. Together with our previous report [38], these findings provide further indications that some actions of SOCE proteins may be sex-dependent.…”

Section: Discussionsupporting

confidence: 86%

“…To explore further the role of neuronal SOCE (nSOCE), we have recently created several transgenic mouse lines that overproduce SOCE proteins specifically in brain neurons. Using these mice, we have shown that the activities of ORAI1 and STIM1 may regulate basal synaptic transmission and synaptic plasticity [38,39]. Together with studies by other groups [40][41][42][43][44], our results show that SOCE proteins play a role in fundamental neuronal processes.…”

Section: Discussionsupporting

confidence: 75%

“…Quantitative Real-Time PCR confirmed specific expression of the transgene in the brain within the established FVB/NJ-Tg(STIM2)Ibd lines. Generation of the FVB/NJ-Tg(ORAI1)Ibd line was described elsewhere [38]. Double transgenic mice were generated by crossing homozygotes of male FVB/NJ-Tg(STIM2)Ibd with the female FVB/NJ-Tg(ORAI1)Ibd.…”

Section: Generation Of Fvb/nj-tg(stim2/orai1)ibd Transgenic Micementioning

confidence: 99%

“…The tests were described extensively elsewhere [38,39]. In brief, in the rotarod test the mice were forced to maintain their balance on a rotating rod (30 mm diameter) that was placed 20 cm above the apparatus floor.…”

Section: Behavioral Analysismentioning

confidence: 99%

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Transgenic Mice Overexpressing Human STIM2 and ORAI1 in Neurons Exhibit Changes in Behavior and Calcium Homeostasis but Show No Signs of Neurodegeneration

Majewski

Maciąg

Boguszewski

et al. 2020

IJMS

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The maintenance of proper cytosolic Ca2+ level is crucial for neuronal survival, and dysregulation of Ca2+ homeostasis is found in a variety of neurological disorders, including Alzheimer’s disease. According to the “Ca2+ hypothesis of aging”, Ca2+ disturbances precede the onset of AD symptoms and lead to neurodegeneration. STIM and ORAI proteins are involved in neuronal physiological and pathological processes as essential components of the store-operated Ca2+ entry. Our previous data suggested that overexpression of STIM2 and ORAI1 might increase basal neuronal cytosolic Ca2+ level. We generated double transgenic mice overexpressing these two genes in neurons, expecting that the increased basal Ca2+ concentration will lead to premature neurodegeneration. We observed changes in Ca2+ homeostasis and electrophysiological properties in acute brain slices of STIM2/ORAI1 neurons. However, we did not observe any augmentation of neurodegenerative processes, as tested by Fluoro-Jade® C staining and assessment of amyloidogenesis. The battery of behavioral tests did not show any signs of accelerated aging. We conclude that changes of calcium homeostasis induced by overexpression of STIM2 and ORAI1 had no substantial adverse effects on neurons and did not lead to early neurodegeneration.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 75%

Section: Generation Of Fvb/nj-tg(stim2/orai1)ibd Transgenic Micementioning

confidence: 99%

Section: Behavioral Analysismentioning

confidence: 99%

See 2 more Smart Citations

Transgenic Mice Overexpressing Human STIM2 and ORAI1 in Neurons Exhibit Changes in Behavior and Calcium Homeostasis but Show No Signs of Neurodegeneration

Majewski

Maciąg

Boguszewski

et al. 2020

IJMS

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“…Our recently published results indicate that overexpression of ORAI1 in the murine brain leads to spontaneous occurrence of seizure-like events in aged animals [32]. In the present study, we extended the phenotyping of the established transgenic line overexpressing ORAI1 in neurons (FVB/NJ-Tg(ORAI1)Ibd; Nencki Institute of Experimental Biology) by the analysis of Ca 2+ response in the hippocampal CA1 pyramidal cells and RNA sequencing (RNAseq) gene expression profiling.…”

Section: Introductionmentioning

confidence: 93%

Changes in Calcium Homeostasis and Gene Expression Implicated in Epilepsy in Hippocampi of Mice Overexpressing ORAI1

Majewski

Wojtaś

Maciąg

et al. 2019

IJMS

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Previously, we showed that the overexpression of ORAI1 calcium channel in neurons of murine brain led to spontaneous occurrence of seizure-like events in aged animals of transgenic line FVB/NJ-Tg(ORAI1)Ibd (Nencki Institute of Experimental Biology). We aimed to identify the mechanism that is responsible for this phenomenon. Using a modified Ca2+-addback assay in the CA1 region of acute hippocampal slices and FURA-2 acetomethyl ester (AM) Ca2+ indicator, we found that overexpression of ORAI1 in neurons led to altered Ca2+ response. Next, by RNA sequencing (RNAseq) we identified a set of genes, whose expression was changed in our transgenic animals. These data were validated using customized real-time PCR assays and digital droplet PCR (ddPCR) ddPCR. Using real-time PCR, up-regulation of hairy and enhancer of split-5 (Hes-5) gene and down-regulation of aristaless related homeobox (Arx), doublecortin-like kinase 1 (Dclk1), and cyclin-dependent kinase-like 5 (Cdkl5, also known as serine/threonine kinase 9 (Stk9)) genes were found. Digital droplet PCR (ddPCR) analysis revealed down-regulation of Arx. In humans, ARX, DCLK1, and CDLK5 were shown to be mutated in some rare epilepsy-associated disorders. We conclude that the occurrence of seizure-like events in aged mice overexpressing ORAI1 might be due to the down-regulation of Arx, and possibly of Cdkl5 and Dclk1 genes.

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AMPK role in epilepsy: a promising therapeutic target?

Qi,

Zhang,

Gao

et al. 2023

J Neurol

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Behavioral and electrophysiological changes in female mice overexpressing ORAI1 in neurons

Cited by 13 publications

References 88 publications

Transgenic Mice Overexpressing Human STIM2 and ORAI1 in Neurons Exhibit Changes in Behavior and Calcium Homeostasis but Show No Signs of Neurodegeneration

Transgenic Mice Overexpressing Human STIM2 and ORAI1 in Neurons Exhibit Changes in Behavior and Calcium Homeostasis but Show No Signs of Neurodegeneration

Changes in Calcium Homeostasis and Gene Expression Implicated in Epilepsy in Hippocampi of Mice Overexpressing ORAI1

AMPK role in epilepsy: a promising therapeutic target?

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