Talk: MicroRNAs in the interface between inflammation and neurodegeneration

Abstract

By targeting transcriptional or other regulator genes, microRNAs can affect neuron-glia and/or brain-to-body signaling, modifying cognitive states. Given that acetylcholine (ACh) suppresses both anxiety and inflammation, microRNAs could co-modulate neuronal and immune functions by silencing multiple and partially overlapping cholinergic target genes. For example, stress-inducible increases in microRNAs targeted to the 3'-untranslated region of the acetylcholinesterase (AChE) transcripts (e.g. miR-132) can elevate cholinergic signaling and limit cytokines production and brain penetration. This would attenuate the activation of cytokine-responding neurons, affect higher brain functions and resolve damages to neurotransmission, plasticity and cognitive reactions.  Inversely, the sharp decline of miR-132 in the Alzheimer’s disease brain may associate with cognitive deterioration and explain the limited decrease in AChE in the diseased brain in spite of massive losses of cholinergic neurons. Correspondingly, we discovered miR-132 increases in both intestinal inflammation and post-stress anxiety, and observed anxiety and inflammation-associated changes in AChE-targeted miRs in peripheral tissues of healthy volunteers and post-stroke patients and model mice. These may become disease biomarkers and therapeutic interference targets for regaining homeostasis, yielding novel biomedical insights in the neuro-immune interface.