Project Details
Projekt
Deciphering the non coding RNAs linked to cognitive aging.
Applicant
Professor Dr. André Fischer
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Term
from 2014 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 255304912
There is emerging evidence that epigenetic processes including the action of non-coding RNAs provide to brain cells a molecular tool to transform transient environmental stimuli into long-term adaptive changes. An important class of non-coding RNAs are microRNAs (miRs) that bind to their mRNA targets and thereby inhibit gene-expression. Our lab was one of the first to study the complete hippocampal microRNAome using next-generation sequencing approaches (NGS) and could identify via subsequent mechanistic analysis miRs that play a role in memory function and Alzheimers disease. In the previous funding period we suggested two lines of research. First we planed to study the role of miRs linked to healthy aging by correlating the brain microRNAome with changes in cognitive performance using mice as model organism. In a second approach we suggested to study the role of miRs in environmental enrichment (EE), a process that improves memory function and is considered a non-drug based approach to protect individuals from age-associated cognitive decline. We have identified a number of miRs that were linked to age-associated memory decline in mice and humans and began to elucidate the role of these miRs in brain function. By this we were for example able to provide that miR-181a is key regulator of memory function in mice and humans. With respect to the EE project we were able to show that EE not only improved memory function in the enriched mice but also provides a cognitive advantage to the next generation. We demonstrate that this transgenerational inheritance is mediated via RNA in gametes and provide first evidence that miRs such as the miR132/212 cluster contribute to this effect. In the second funding period we will build on these findings and perform further mechanistic studies and also plan to extend our approach to other non-coding RNAs such as lncRNA and circRNAs.
DFG Programme
Priority Programmes
