In Vivo Reprogramming Ameliorates Aging Features in Dentate Gyrus Cells and Improves Memory in Mice
Authors: Félix Hernández
Alberto Rodríguez-Matellán
Noelia Alcazar
Jesús Ávila
Manuel Serrano
Journal: Stem Cell Reports (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Yamanaka factors; adult neurogenesis; aging; cellular reprogramming; doublecortin
Affiliations: Department of Molecular Neuropathology, Centro de Biología Molecular Severo Ochoa, CBMSO, CSIC-UAM, Madrid, Spain; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain., Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain. Electronic address: ., Department of Molecular Neuropathology, Centro de Biología Molecular Severo Ochoa, CBMSO, CSIC-UAM, Madrid, Spain; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Madrid, Spain. Electronic address: .

Abstract:  Post-translational epigenetic modifications take place in mouse neurons of the dentate gyrus (DG) with age. Here, we report that age-dependent reduction in H3K9 trimethylation (H3K9me3) is prevented by cyclic induction of the Yamanaka factors used for cell reprogramming. Interestingly, Yamanaka factors elevated the levels of migrating cells containing the neurogenic markers doublecortin and calretinin, and the levels of the NMDA receptor subunit GluN2B. These changes could result in an increase in the survival of newborn DG neurons during their maturation and higher synaptic plasticity in mature neurons. Importantly, these cellular changes were accompanied by an improvement in mouse performance in the object recognition test over long time. We conclude that transient cyclic reprogramming in vivo in the central nervous system could be an effective strategy to ameliorate aging of the central nervous system and neurodegenerative diseases. 

Retracted: No

PubPeer comments:
 Figure 1A and 2A u2013 S6k bands are more similar than expected ![file] , 
 Thanks. We re on it. Elliott Ross , 
 The blots for total S6K in Fig. 1a are incorrect due to confusion over file names. We will send a correction to JBC as soon as we get info on formatting. Those files were not used for calculations so bar graph data are OK. Fig. 2 is OK. , 
 A corrected version of Fig. 1A was submitted to JBC today along with documentation of file provenance. The corrected figure was accepted by JBC on 5 13 20. , 
 #1 The correction was published https: www.jbc.org content 295 26 8868.short , 
 2020 correction. https: www.jbc.org content 295 26 8868.short In the originally published Fig. 1A, the immunoblots for total S6K were an inadvertent copy of the S6K immunoblots in Fig. 2A. The mistake was caused by confusion over file names during creation of the figure. This error has now been corrected. The bar graphs in the original Fig. 1, B and C, are based on quantitation of multiple blots and are correct as shown. This correction does not affect the results or conclusions of this work. ,