Abstract
Lithium (Li) is a medication long-used to treat bipolar disorder. It is currently under investigation for multiple CNS disorders, including Alzheimer’s disease (AD). While perturbation of RNA levels by Li was reported, its effects on the whole-transcriptome remains unexplored. We, therefore, sought to determine comprehensive effects of Li treatment on RNA levels.
Highlights
Lithium (Li) has been used to effectively treat bipolar disorder for more than 60 years[1]
We found that Li changes expression of multiple small RNA species, non-coding small nucleolar RNAs, in all-trans retinoic acid (ATRA) differentiated human neuroblastoma neuronal (SK-N-SH) culture, but that small RNA species do not all respond to Li stimulation
Small RNAs, small nucleolar RNAs are over-represented among Li-influenced genes
Summary
Lithium (Li) has been used to effectively treat bipolar disorder for more than 60 years[1]. Li increases N-acetyl-aspartate levels in human brain (a measure of neuronal viability) during therapeutic treatment, as measured by magnetic resonance spectroscopy[25]. This increase appears to be related to increases in grey matter volume[26]. Changes in adult neuronal cells from Li-responsive patients may be related to decreased phosphorylation of collapsin response mediator protein-2 (CRMP2) and increased dendritic spine density[31]. Gene expression changes induced by Li treatment exist in both neuronal cultures and animals[32,33,34,35] Those reports were array-based assays, not whole transcriptome surveys. Our results generated interaction networks that can inform future mechanistic research, relevant to AD, bipolar and other neuropsychiatric disorders
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