Figure 3.

Isx-9 up-regulates adult neurognesis through a cell-intrinsic Mef2-dependent mechanism. A–C) Cells from nestin-GFP mice were sorted (FACS), and their RNA was amplified, reverse-transcribed, and used for a gene chip (A, B) or qPCR (C). Data analysis identified several biofunctions where most transcripts showed altered relative expression levels by Isx-9 (B). Isx-9-induced up-regulation of Mef2c was detected via microarray (data not shown) and confirmed via qPCR (C). D) To assess whether Mef2 was necessary for Isx-9-induced enhancement of adult hippocampal neurogenesis, nestin-CreER^T2/R26R-YFP-WT, Mef2a/d^flox/flox or Mef2a/c/d^flox/flox transgenic mice were given Tam to induce Cre-mediated recombination and then given Veh or Isx-9. E) Representative photomicrographs show YFP⁺ DG cells in mice that are Mef2-WT (left column), Mef2a/d-KO (middle column), and Mef2a/c/d-KO (right column) 12 d after 7 d administration of Veh (top panels) or Isx-9 (bottom panels). Scale bars = 50 μm. F) While Isx-9 did not change YFP⁺ cell numbers in Mef2-WT mice, it significantly decreased YFP⁺ cell numbers in Mef2a/c/d-KO mice. G, H) Isx-9 increased YFP⁺ neuron numbers in Mef2-WT mice, but decreased YFP⁺ neuron numbers in Mef2a/c/d-KO mice (G) without changing YFP⁺ Type-1 cell numbers in any group (H). n.s., not significant (P>0.05). *P < 0.05, **P < 0.01; paired t test.