Memory Decline and Its Reversal in Aging and Neurodegeneration Involve miR-183/96/182 Biogenesis.

Aging is characterized by progressive memory decline that can lead to dementia when associated with neurodegeneration. Here, we show in mice that aging-related memory decline involves defective biogenesis of microRNAs (miRNAs), in particular miR-183/96/182 cluster, resulting from increased protein phosphatase 1 (PP1) and altered receptor SMAD (R-SMAD) signaling. Correction of the defect by miR-183/96/182 overexpression in hippocampus or by environmental enrichment that normalizes PP1 activity restores memory in aged animals.

Interplay between TETs and microRNAs in the adult brain for memory formation.

5-hydroxymethylation (5-hmC) is an epigenetic modification on DNA that results from the conversion of 5-methylcytosine by Ten-Eleven Translocation (TET) proteins. 5-hmC is widely present in the brain and is subjected to dynamic regulation during development and upon neuronal activity. It was recently shown to be involved in memory processes but currently, little is known about how it is controlled in the brain during memory formation.

The microRNA cluster miR-183/96/182 contributes to long-term memory in a protein phosphatase 1-dependent manner.

Memory formation is a complex cognitive function regulated by coordinated synaptic and nuclear processes in neurons. In mammals, it is controlled by multiple molecular activators and suppressors, including the key signalling regulator, protein phosphatase 1 (PP1). Here, we show that memory control by PP1 involves the miR-183/96/182 cluster and its selective regulation during memory formation.