Long non-coding RNAs potentially suppressive for brain perivascular astrogliosis induced by environmental ultrafine particulate matter

Respiratory exposure to low doses of environmental ultrafine particulate matter induces perivascular astrogliosis lesions in the cerebral cortex, associated with neurodegenerative and neurodevelopmental disorders. Proteins with abnormal secondary structures accumulate in such lesions during conditions such as dementia. In addition to the upregulation of glial fibrillary acidic protein (Gfap) and aquaporin 4 (Aqp4) genes involved in pathogenesis, several long non-coding RNAs (lncRNAs) are differentially expressed in the lesion; however, their functions remain unclear. This study aimed to explore the potential roles of lncRNAs in suppressing perivascular lesions. RNA expression profiles of the cerebral cortex of 6-week-old mice with perivascular lesions were analyzed using principal component analysis to identify lncRNAs whose expression was inversely correlated with the lesion severity. Common sequences among these lncRNA groups and associated mRNAs with their complementary regions were identified. Identified mRNAs were analyzed using the DAVID functional enrichment tool. A shared sequence, "AUCAUCUUUCC," was found in potentially lesion-suppressive lncRNAs inversely correlated with lesion extent. The complementary mRNAs were enriched in eight Gene Ontology terms, including "Cell projection," "Dendrites," "Synapses," and "Projection neurons," related to astrocytic endfoot elongation observed in the perivascular lesions and in neural functions in the brain. The identified lncRNAs and their common sequences may represent novel regulators of cellular development and lesion dynamics. The potential of RNA molecules with this sequence to modulate the pathogenesis of neurodegenerative and neurodevelopmental disorders warrants further investigation.