IJMS, Vol. 21, Pages 842: Transgenic Mice Overexpressing Human STIM2 and ORAI1 in Neurons Exhibit Changes in Behavior and Calcium Homeostasis but Show No Signs of Neurodegeneration (International Journal of Molecular Sciences)

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+ item. 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.