Hippocampal demyelination and memory dysfunction are associated with increased levels of the neuronal microRNA miR-124 and reduced AMPA receptors

The researchers explored if loss of hippocampal myelin alters expression of neuronal microRNAs (miRNAs), by comparing miRNA profiles from myelinated and demyelinated hippocampi from post-mortem MS brains and performed validation studies. MiRNAs are critical regulators of the development and maturation of neurons and oligodendrocytes. 

The results showed that hippocampal demyelination leads to an up-regulation of several neuronal miRNAs, including miR-124 and reduced mRNA and protein levels of AMPA receptors (glutamate receptors) in demyelinated hippocampus. Hippocampal demyelination in mice also increased miRNA-124, reduced expression of AMPA receptors, and decreased memory performance in water maze tests. Remyelination of the mouse hippocampus reversed these changes. Therefore, this data highlights how myelin can influence neuronal gene expression by regulating levels of neuronal miRNAs. This raises the possibility that selective inhibition of miR-124 in hippocampal neurons could enhance cognitive performance in MS patients.

Authors: Dutta R, Chomyk AM

Source: Ann Neurol. 2013 Feb 11. doi: 10.1002/ana.23860. [Epub ahead of print]

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