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Dep. For Psychiatry and Psychotherapy University Medical Center German Center for Neurodegenerative
Grisebachstr. 5, 37077 Göttingen (Germany)
Phone : +49 551 3910378
Fax : +49 551 399836
E-Mail : firstname.lastname@example.org
Web : See online here
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 Alzheimer’s disease. In this project we aim to provide mechanistic insight to the role miRs in memory function during cognitive aging. More specifically we plan to map the microRNAome in the aging hippocampus and prefrontal cortex which will be followed by a computational analysis to decipher microRNA signatures linked to cognitive aging. We will then use mechanistic studies to assay the role of key microRNAs in memory function and synaptic plasticity. Similar experiments will be performed in response to an environmental enrichment training conclusion which is known to ameliorate cognitive decline. Our data will help to decipher the role of microRNAome dynamics in the adult brain and might have direct impact on therapeutic strategies to treat dementia.
Some key technologies for internal use :
- Behavior testing of mice
- Small RNAseq
- Bioinformatic analysis of smallRNAseq data (differential expression, machine learning)
- In vivo manipulation of microRNA
- Adeno associated viruses
Stilling, R.M, Benito, E., Gertig, M., Capece, V., Barth, J., Burkhardt, S., Bonn, S., Fischer, A. De-regulation of gene expression and alternative splicing affects distinct cellular pathways in the aging hippocampus. Frontiers in Cellular Neuroscience, 8:373. eCollection 2014.
Fischer, A. Epigenetic Memory: The lamarckian brain, EMBO J. 2014 Epub ahead of print
Stilling, R.M., Rönicke, R. , Benito, E., Urbanke, H. Capece, V., Burkhardt, S. Bahari-Javan, S., Barth, J., Sananbenesi, F., Schütz, A.L., Dyczkowski, J., Martinez-hernandez, a., kerimoglu, c., dent, S.Y.R., Bonn, S., Reymann, K.G., Fischer. A. K-lysine acetyltransferase 2a regulates a hippocampal gene-expression network linked to memory formation. EMBO J. 33, 17, 1912-1927
Rao P, Benito E, Fischer A. MicroRNAs as biomarkers for CNS disease. Front Mol Neurosci. 2013 Nov 26;6:39. eCollection 2013.
Zovoilis A, Agbemenyah HY, Agis-Balboa RC, Stilling RM, Edbauer D, Rao P, Farinelli L, Delalle I, Schmitt A, Falkai P, Bahari-Javan S, Burkhardt S, Sananbenesi F, Fischer A. microRNA-34c is a novel target to treat dementias. EMBO J. 2011 Sep 23;30(20):4299-308. doi: 10.1038/emboj.2011.327.