An integrative analysis of miRNA and mRNA expression in the brains of Alzheimer's disease transgenic mice after real-world PM2.5 exposure

Fine particulatematter (PM2.5) is associated with increased risks of Alzheimer’s disease (AD),yet the toxicologicalmechanisms of PM2.5 promoting AD remain unclear. In this study,wildtype and APP/PS1 transgenic mice (AD mice) were exposed to either filtered air (FA) or PM2.5 for eight weeks with a real-world exposure system in Taiyuan, China (mean PM2.5 concentration in the cage was 61 μg/m3). We found that PM2.5 exposure could remarkably aggravate AD mice’s ethological and brain ultrastructural damage, along with the elevation of the pro-inflammatory cytokines (IL-6 and TNF-α), Aβ-42 and AChE levels and the decline of ChAT levels in the brains. Based on high-throughput sequencing results, some differentially expressed (DE) mRNAs and DE miRNAs in the brains of AD mice after PM2.5 exposure were screened.Using RT-qPCR, seven DEmiRNAs (mmu-miR-193b-5p, 122b-5p, 466h-3p, 10b-5p, 1895, 384–5p, and 6412) and six genes (Pcdhgb8, Unc13b, Robo3, Prph, Pter, and Tbata) were evidenced the and verified. Two miRNA-target gene pairs (miR-125b-Pcdhgb8 pair and miR-466h-3p-IL-17Rα/TGF-βR2/Aβ-42/AChE pairs) were demonstrated that they were more related to PM2.5-induced brain injury. Results of Gene Ontology (GO) pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways predicted that synaptic and postsynaptic regulation, axon guidance, Wnt, MAPK, and mTOR pathways might be the possible regulatory mechanisms associated with pathological response. These revealed that PM2.5- elevated pro-inflammatory cytokine levels and PM2.5-altered neurotransmitter levels in AD mice could be the important causes of brain damage and proposed the promising miRNA andmRNA biomarkers and potentialmiRNA-mRNA interaction networks of PM2.5-promoted AD.     

Phylogeographic structure of false clownfish, Amphiprion ocellaris, explained by sea level changes on the Sunda shelf

The phylogenetic structure of the anemonefish Amphiprion ocellaris was established based on sequence data generated for the 5′ end of the cytochrome b (cytb) gene at 11 sites throughout Southeast Asia. Considerable genetic structuring was observed throughout the range of A. ocellaris. The region has a complex geography, with the Sunda shelf having been exposed during the lower sea levels associated with periods of glaciation. The direction of subsequent flooding of the Sunda shelf, as a direct consequence of the retreating glacial sheets, can be predicted based on the major river drainage systems in the region. Much of the phylogeographic structure, including levels of intra-site genetic variation, can be explained in terms of the “seeding” of sites on the Sunda shelf, by those on the shelf rim, as sea levels rose. We often found surface ocean currents in the region, which should influence larval dispersal, to be poorly correlated with phylogeographic structure. Several geographically close sites, which appear to be connected by surface currents, showed significant genetic stratification. We hypothesise that the phylogeographic structure of A. ocellaris is more reminiscent of the Pleistocene sea level changes than surface currents. The high contribution of sea level changes to the phylogeographic structure was also supported by several missing haplotypes in the generated spanning network. Cytb DNA sequences generated for recently recruited A. ocellaris individuals sampled from Singapore indicate that, on a local scale, there is a directional inflow of recruits, which is dependent on the monsoon seasons. The nature of dispersal and genetic structure of reef fish species found on the Sunda shelf is clearly complex, and should take into consideration past phylogeographic events. Received: 13 November 1999 / Accepted: 12 July 2000