Generation of a neuro-specific microarray reveals novel differentially expressed noncoding RNAs in mouse models for neurodegenerative diseases

Abstract

We have generated a novel, neuro-specific ncRNA microarray, covering 1472 ncRNA species, to investigate their expression in different mouse models for central nervous system diseases. Thereby, we analyzed ncRNA expression in two mouse models with impaired calcium channel activity, implicated in Epilepsy or Parkinson's disease, respectively, as well as in a mouse model mimicking pathophysiological aspects of Alzheimer's disease. We identified well over a hundred differentially expressed ncRNAs, either from known classes of ncRNAs, such as miRNAs or snoRNAs or which represented entirely novel ncRNA species. Several differentially expressed ncRNAs in the calcium channel mouse models were assigned as miRNAs and target genes involved in calcium signaling, thus suggesting feedback regulation of miRNAs by calcium signaling. In the Alzheimer mouse model, we identified two snoRNAs, whose expression was deregulated prior to amyloid plaque formation. Interestingly, the presence of snoRNAs could be detected in cerebral spine fluid samples in humans, thus potentially serving as early diagnostic markers for Alzheimer's disease. In addition to known ncRNAs species, we also identified 63 differentially expressed, entirely novel ncRNA candidates, located in intronic or intergenic regions of the mouse genome, genomic locations, which previously have been shown to harbor the majority of functional ncRNAs.

Transcriptomic Profiling of Extracellular RNAs Present in Cerebrospinal Fluid Identifies Differentially Expressed Transcripts in Parkinson’s Disease

“…Our RNA-seq data and bioinformatics pipeline suggest that extracellular RNAs might be detectable in CSF and their presence and differential expression can be monitored to identify Parkinson’s disease-related extracellular RNAs. We observed higher frequency of non-coding RNAs in the CSF of PD patients compared to controls corroborating previous reports that various ncRNA species perform essential functions in the regulation of gene expression during neural development, plasticity, and aging [ 20, 21 ]. Several ncRNAs are implicated in PD [ 22 ] and other CNS diseases.…”

Calcium signals regulated by NAADP and two-pore channels - their role in development, differentiation and cancer

“…While past studies have focused on the Ca 2+ -dependent modulation of protein effectors, it is now becoming clear that Ca 2+ signals can also modulate expression and activity of ncRNAs such as microRNAs (Choi et al, 2014, Gstir et al, 2014, Harada et al, 2014, increasingly recognised as important players in the control of gene expression during embryonic development, by regulating processes such as cell proliferation, differentiation and apoptosis (Moreno-Moya et al, 2014).…”

Integrative analysis of an lncRNA‑associated competing endogenous RNA network in human trabecular meshwork cells under oxidative stress

“…lncRNAs play a significant role in regulating gene expression, protein modification, cell differentiation, immune response and other critical biochemical pathways (14,15). Studies have identified roles for lncrnas in several neurodegenerative diseases, such as Alzheimer's, Parkinson's and Huntington's disease (16)(17)(18)(19). in 2011, a hypothesis was proposed, which suggested that lncrnas were microrna (mirna) sponges that suppressed mirna interactions with mrnas and affected translation of protein-coding genes (20).…”