Transcriptomic evaluation of Mef2c manipulation in the mouse brain and HT22 cells

ABSTRACT: The objective of this study is to elucidate the transcriptomic mechanisms underlying Mef2c-regulated cognitive aging and to determine whether intact Mef2c signaling is required for the antiaging transcriptomic effects of Dasatinib plus Quercetin (D+Q) and Spermidine (SPD). To evaluate its physiological impact, we manipulated Mef2c expression in the mouse brain using lentiviral vectors and performed transcriptomic profiling. In 19-month-old aged mice, overexpressing Mef2c (Mef2c OE) upregulated genes enriched in learning, memory, and neuron differentiation, while effectively repressing stress-activated signaling and chemokine production. Conversely, knocking down Mef2c (siMef2c) in 11-month-old middle-aged mice induced a transcriptomic shift towards heightened oxidative stress and neuronal death, coupled with the suppression of cognition and synaptic transmission pathways. Furthermore, to evaluate whether silencing Mef2c abolishes the observed antiaging effects of D+Q and SPD in cultured neurons, we pre-treated HT22 cells with siMef2c followed by D+Q or SPD administration. Transcriptomic profiling revealed that under conditions of Mef2c depletion, neither D+Q nor SPD could elicit the antiaging transcriptomic signatures previously observed in the brain. This confirms that an intact Mef2c signaling is indispensable for their full neuroprotective actions.

ORGANISM(S): Mus musculus

PROVIDER: GSE336018 | GEO | 2026/08/30

REPOSITORIES: GEO