Stress Reactions Orchestrate Parasympathetic Functioning and Inflammation Under Diverse Cholinergic Manipulations

Stress reactions impair parasympathetic functioning, elevate inflammation, and modify brain microRNAs (miRNA) via cholinergic genes and their targeting miRNAs (CholinomiRs), and newer technologies may provide novel pharmaceutic avenues to these issues. Here, we describe stress-inducible changes in the expression of cholinergic genes (muscarinic, nicotinic, cholinesterases, etc.), which result in rapid increases of cholinergic signaling, and demonstrate how surveillance by CholinomiRs provides fine-tuning of these changes in cholinergic signaling, retrieving homeostasis. This chapter focuses on miRNA-132 (an evolutionarily conserved acetylcholinesterase (AChE) targeting miRNA), and its role in stress and inflammation, both of which upregulate miRNA-132 in the mammalian brain, potentiate the cholinergic tone, and suppress inflammation by downregulating AChE. Future technologies, including the use of chemically protected antisense oligonucleotides (e.g., anti-miRNA-132) may open new ways to suppress the levels of miRNAs involved in stress and inflammation. The delicate balance between stress and inflammation and ways to retrieve it thus merits renewed discussion.