S-022
Audiovisual Stimulation at 40 Hz Induces Cell Type–Specific Transcriptional Changes in the Aged Dentate Gyrus
Juan Simón Serrangeli1, Natalí Rasetto1, Ariel Berardino2, Daniela Di Bella3, Paola Arlotta3, Ariel Chernomoretz2, Alejandro Schinder1, Mariela Trinchero1
  1. 1. Laboratory of Neuronal Plasticity, Leloir Institute (IIBBA-CONICET); Buenos Aires, Argentina
  2. 2. Laboratory of Integrative Systems Biology, Leloir Institute (IIBBA-CONICET); Buenos Aires, Argentina
  3. 3. Department of Stem Cells and Regenerative Biology, Harvard University and Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
Presenting Author:
Juan Simón Serrangeli
juansserrangeli@gmail.com
Neurogenesis persists in the dentate gyrus throughout life, but declines sharply with aging. We have recently shown that 40 Hz audiovisual stimulation (AuViS) enhances activity in the aged dentate gyrus and promotes neurogenesis in middle-aged mice. These effects may be related with changes within the neurogenic niche, yet the underlying cellular and molecular mechanisms remain unclear. We hypothesized that AuViS-induced cellular modifications are driven by transcriptional changes in the aged neurogenic niche. To test this idea, we performed single-nuclei RNA sequencing of the dentate gyrus from 8-month-old mice exposed to 6 weeks of AuViS or control conditions. Notably, the most significant change was the transcriptional upregulation of tight junction–related genes such as Cldn5 in endothelial cells, suggesting enhanced blood–brain barrier (BBB) integrity. In contrast, neuronal populations displayed only subtle changes in gene expression. These results reveal that AuViS elicits cell type-specific transcriptional responses and point to BBB remodeling as a potential mechanism contributing to enhanced neurogenesis in the aged dentate gyrus.