Induction of neostriatal neurogenesis slows disease progression in a transgenic murine model of Huntington disease
J. Clin. Invest. Sung-Rae Cho, et al. 117:2889 doi:10.1172/JCI31778 [Go to this article.]

Figure 3
New neurons were the product of antecedent neuronal mitogenesis. (A) Schematic of a mouse brain section through the striatum (STR) and lateral ventricle (LV) showing the locations of images in B–H (asterisks). CC, corpus callosum. (B) Striatal ventricular wall of an AdBDNF/AdNoggin-treated R6/2 mouse, given BrdU for 3 wk after viral injection at 6 wk of age and sacrificed at 10 wk, immunostained for BrdU (green), βIII-tubulin (red), and Ki67 (blue), which is expressed by mitotically active cells. In the subventricular zone, actively dividing subependymal cells expressed Ki67, whereas BrdU⁺ daughter cells, the products of earlier divisions, did not. In the neostriatum within the same section, newly generated BrdU⁺ neurons identified by βIII-tubulin (C) or NeuN (D) did not express Ki67 and thus showed no evidence of either persistent mitotic competence or aberrant cell cycle reentry. To the contrary, newly generated BrdU⁺βIII-tubulin⁺ (E) and BrdU⁺NeuN⁺ (F) neurons expressed the tumor suppressor p27^kip1 (blue, E and F), a marker of mitotic quiescence. A cohort of BrdU⁺ cells in AdBDNF/AdNoggin-treated mice coexpressed the developmental migratory neuroblastic marker DCX (red, G and H); importantly, these BrdU⁺DCX⁺ cells were not found in AdNull-treated R6/2 striata at this age, indicating that the immigration of migrating neuroblasts into the R6/2 striatum was a function of AdBDNF/AdNoggin treatment. Scale bars: 10 μm (B–F); 5 μm (G and H).