Dialing Up an miRNA’s Expression Calms Neurons, Reduces Seizures
A particular miRNA, miR-128, is not only abundantly expressed in the brains of animals and humans, it is also known as a fine-tuner of gene expression. Nonetheless, when scientists investigated miR-128’s role in gene silencing and regulation, dialing this noncoding RNA’s expression up and down, even they were surprised to find that miR-128 could, on its own, control complex functions in the adult brain.
The scientists, based at the Icahn School of Medicine at Mount Sinai, found that miR-128 regulates motor activity by modulating neuronal signaling networks and excitability. They also found that miR-128 governs motor activity by suppressing the expression of various ion channels and signaling components of a particular enzyme, extracellular signal-regulated kinase 2 (ERK2). ERK2 controls how responsive neurons are to various signals in the body.
The scientists described their findings in an article entitled “MicroRNA-128 Governs Neuronal Excitability and Motor Behavior in Mice.” The article, appearing online in Science and dated December 6, also suggests that targeting the microRNA signaling pathway might benefit patients suffering severe epilepsy or other movement disorders.
In their investigation, the scientists engineered mice to express miR-128 at various levels. Mice that underexpressed miR-128 showed a dose-dependent decrease in motor activity and fatal epilepsy. Mice that overexpressed miR-128 showed lower neuronal responsiveness and susceptibility to seizures. In addition, motor activity was reduced, as were motor difficulties associated with Parkinson’s-like disease.
According to the authors, bioinformatics network and pathway analyses of the miR-128 target genes indicate the ability of miR-128 to affect molecular processes that are intrinsically linked to the regulation of neuronal excitability and motor behavior in mice and humans.
In their article, the authors wrote, “The human miR-128-2 gene on chromosome 3p lies within a region that has been linked to idiopathic generalized epilepsy. It is tempting to speculate that changes in miR-128 or miR-128 gene expression could be a potential cause of increased neuronal excitability and epilepsy in humans. Our understanding of miR-128’s role in neuronal signaling could prove advantageous in the design of novel therapeutics for epilepsy and motor disorders.”