GSE158513
Purkinje neurons with loss of STIM1 exhibit age-dependent changes in gene expression and synaptic components
The Stromal interaction molecule 1 (STIM1) is an ER-Ca2+ sensor and an essential component of ER-Ca2+ store operated Ca2+entry (SOCE). Loss of STIM1 affects metabotropic Glutamate Receptor 1 (mGluR1) mediated synaptic transmission, neuronal Ca2+ homeostasis and intrinsic plasticity in Purkinje Neurons (PNs). Long-term changes of intracellular Ca2+ signaling in PNs lead to neurodegenerative conditions, as evident in individuals with mutations of the ER-Ca2+ channel, the Inositol, 1,4,5-triphosphate receptor (IP3R). Moreover, Changes in gene expression upon reduced SOCE in non-excitable immune cells, the developing mouse brain, Drosophila pupal neurons  and human neural precursor cells have been reported. Gene expression profiles of mature differentiated neurons with loss of STIM1/nSOC have not been published to date. The study evaluated the differential gene expression in STIM1 knockout purkinje neurons compared to wild type purkinje neurons from 1 year old mice. Analysis of gene expression profiles demonstrated that STIM1 dependent Ca2+ homeostasis and signaling helps to maintain the expression of multiple key components of synaptic architecture and function in ageing animals. Our findings are significant in the context of finding new therapeutic means of alleviating the neurodegenerative changes associated with human SCAs. Overall design: RNA isolated from the microdissected purkinje neuronal layer and molecular layer followed by RNA sequencing using Illumina Hiseq 2500 platform. Three biological replicates each of wild type and  STIM1 knockout purkinje neurons of 1 year old mice was used for the experiment.