Cellular and Molecular Neurobiology
Author: Magalí Herrero | email: mherrero@leloir.org.ar
Magalí Herrero 1°, Natalí B. Rasetto 1°, Damiana Giacomini 1°, Ariel Berardino 2°, Tomás Vega Waichman 2°, Mariela F. Trinchero 1°, Daniela Di Bella 3°, Paola Arlotta 3°, Ariel Chernomoretz 2°, Alejandro F. Schinder 1°
1° Laboratory of Neuronal Plasticity, Leloir Institute-CONICET, Buenos Aires, Argentina.
2° Laboratory of Integrative Systems Biology, Leloir Institute-CONICET, Buenos Aires, Argentina.
3° Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA.
The dentate gyrus of the adult hippocampus has a distinctive plasticity mechanism that consists in the generation and integration of granule cells (GCs) in the preexisting circuit. The development of new GCs takes about 8 weeks and can be divided into 4 phases based on electrophysiological and morphological features. In previous studies we have shown that the development of new neurons is largely delayed in the aging brain. However the molecular basis underlying this slowdown remain unknown. We hypothesized that these maturation stages are driven by changes in the transcriptional program, which can be revealed by transcriptomic analysis. Using high-throughput single nucleus RNA sequencing, our laboratory has generated one data set containing new GCs from young adult mice, and one from neurons born in aging mice. Preliminary bioinformatic analysis allowed us to distinguish defined clusters corresponding to different cell types and neuronal maturation stages. We are currently interrogating the gene expression profile differences between neurons born in young and middle-aged mice in order to investigate the molecular basis underling the protracted development of GCs during aging.