To investigate the potential role of microRNA (miRNA) in the regulation of circadian rhythm, we performed microarray-based expression profiling study of both miRNA and mRNA in mouse liver for 48 h at 4-hour intervals. Circadian miRNA-mRNA target pair is defined as the pair both elements of which show circadian expression patterns and the sequence-based target relationship of which can be predicted. Circadian initiators, Clock and Bmal1, showed inversely correlated circadian expression patterns against their corresponding miRNAs, miR-181d and miR-191, targeting them. In contrast, circadian suppressors, Per, Cry, CKIe and Rev-erba, exhibited positively correlated circadian expression patterns to their corresponding miRNAs. Genomic location analysis revealed that intronic region showed higher abundance of cyclic than non-cyclic miRNAs targeting circadian genes while other (i.e., 3'-UTR, exon and intergenic) regions showed no difference. It is suggested that miRNAs are involved in the regulation of peripheral circadian rhythm in mouse liver by modulating Clock:Bmal1 complex. Identifying specific miRNAs and their targets that are critically involved in circadian rhythm will provide a better understanding of the regulation of circadian-clock system.

Microglial cells, the resident immune cells of the spinal cord, become activated in response to peripheral nerve injury. Microglia activation contributes to the development of neuropathic pain. Here we employed microarray analysis of individually collected pools of 10 spinal microglia cells to identify changes of levels and cell-to-cell expression variance of microglial genes during their activation after peripheral nerve injury. The analysis of microglia on postoperative day 1 (POD1) identified miR-29c as a critical factor for microglial activation and the development of neuropathic pain. Early POD1 microglia exhibited a very distinct expression profile compared to late POD7 microglia, possibly leading to the transition from initiation to maintenance of neuropathic pain. We found sample variance patterns that were consistent with the hypothesis that microglia were highly heterogeneous at the level of individual cells, and variation analysis identified 56 microglial genes potentially linked to the maintenance of neuropathic pain which included Gria1. This study provides insights into spinal microglial biology and reveals novel microglial targets for the treatment of neuropathic pain.