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Gene interactions and pathways from curated databases and text-mining
Eur J Pharmacol 2013, PMID: 23535605

Up-regulation of the canonical Wnt-3A and Sonic hedgehog signaling underlies melanocortin-induced neurogenesis after cerebral ischemia.

Spaccapelo, Luca; Galantucci, Maria; Neri, Laura; Contri, Miranda; Pizzala, Roberto; D'Amico, Roberto; Ottani, Alessandra; Sandrini, Maurizio; Zaffe, Davide; Giuliani, Daniela; Guarini, Salvatore

In experimental cerebral ischemia, melanocortin MC4 receptor agonists induce neuroprotection and neurogenesis with subsequent long-lasting functional recovery. Here we investigated the molecular mechanisms underlying melanocortin-induced neurogenesis. Gerbils were subjected to transient global cerebral ischemia, then they were treated every 12 h, and until sacrifice, with 5-bromo-2'-deoxyuridine (BrdU; to label proliferating cells), and the melanocortin analog [Nle(4),d-Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH) or saline. NDP-α-MSH increased hippocampus dentate gyrus (DG) expression of Wnt-3A, β-catenin, Sonic hedgehog (Shh), Zif268, interleukin-10 (IL-10) and doublecortin (DCX), as detected at days 3, 6 and 10 after the ischemic insult. Further, an elevated number of BrdU immunoreactive cells was found at days 3 and 10, and an improved histological picture with reduced neuronal loss at day 10, associated with learning and memory recovery. Pharmacological blockade of the Wnt-3A/β-catenin and Shh pathways, as well as of melanocortin MC4 receptors, prevented all effects of NDP-α-MSH. These data indicate that, in experimental brain ischemia, treatment with melanocortins acting at MC4 receptors induces neural stem/progenitor cell proliferation in the DG by promptly and effectively triggering the canonical Wnt-3A/β-catenin and Shh signaling pathways. Activation of these pathways is associated with up-regulation of the repair factor Zif268 and the neurogenesis facilitating factor IL-10, and it seems to address mainly toward a neuronal fate, as indicated by the increase in DCX positive cells.

Diseases/Pathways annotated by Medline MESH: Brain Ischemia, Disease Models, Animal, Wnt Signaling Pathway
Document information provided by NCBI PubMed

Text Mining Data

Sonic hedgehog (Shh) → NDP-a-MSH: " NDP-a-MSH increased hippocampus dentate gyrus ( DG ) expression of Wnt-3A, ß-catenin, Sonic hedgehog (Shh) , Zif268, interleukin-10 (IL-10) and doublecortin ( DCX ), as detected at days 3, 6 and 10 after the ischemic insult "

Sonic hedgehog (Shh) → NDP-a-MSH: " NDP-a-MSH increased hippocampus dentate gyrus ( DG ) expression of Wnt-3A, ß-catenin, Sonic hedgehog (Shh) , Zif268, interleukin-10 (IL-10) and doublecortin ( DCX ), as detected at days 3, 6 and 10 after the ischemic insult "

interleukin-10 → NDP-a-MSH: " NDP-a-MSH increased hippocampus dentate gyrus ( DG ) expression of Wnt-3A, ß-catenin, Sonic hedgehog (Shh), Zif268, interleukin-10 (IL-10) and doublecortin ( DCX ), as detected at days 3, 6 and 10 after the ischemic insult "

interleukin-10 → NDP-a-MSH: " NDP-a-MSH increased hippocampus dentate gyrus ( DG ) expression of Wnt-3A, ß-catenin, Sonic hedgehog (Shh), Zif268, interleukin-10 (IL-10) and doublecortin ( DCX ), as detected at days 3, 6 and 10 after the ischemic insult "

Wnt-3A → NDP-a-MSH: " NDP-a-MSH increased hippocampus dentate gyrus ( DG ) expression of Wnt-3A , ß-catenin, Sonic hedgehog (Shh), Zif268, interleukin-10 (IL-10) and doublecortin ( DCX ), as detected at days 3, 6 and 10 after the ischemic insult "

Wnt-3A → NDP-a-MSH: " NDP-a-MSH increased hippocampus dentate gyrus ( DG ) expression of Wnt-3A , ß-catenin, Sonic hedgehog (Shh), Zif268, interleukin-10 (IL-10) and doublecortin ( DCX ), as detected at days 3, 6 and 10 after the ischemic insult "

doublecortin → NDP-a-MSH: " NDP-a-MSH increased hippocampus dentate gyrus ( DG ) expression of Wnt-3A, ß-catenin, Sonic hedgehog (Shh), Zif268, interleukin-10 (IL-10) and doublecortin ( DCX ), as detected at days 3, 6 and 10 after the ischemic insult "

doublecortin → NDP-a-MSH: " NDP-a-MSH increased hippocampus dentate gyrus ( DG ) expression of Wnt-3A, ß-catenin, Sonic hedgehog (Shh), Zif268, interleukin-10 (IL-10) and doublecortin ( DCX ), as detected at days 3, 6 and 10 after the ischemic insult "

interleukin-10 (IL-10) → NDP-a-MSH: " NDP-a-MSH increased hippocampus dentate gyrus ( DG ) expression of Wnt-3A, ß-catenin, Sonic hedgehog (Shh), Zif268, interleukin-10 (IL-10) and doublecortin ( DCX ), as detected at days 3, 6 and 10 after the ischemic insult "

interleukin-10 (IL-10) → NDP-a-MSH: " NDP-a-MSH increased hippocampus dentate gyrus ( DG ) expression of Wnt-3A, ß-catenin, Sonic hedgehog (Shh), Zif268, interleukin-10 (IL-10) and doublecortin ( DCX ), as detected at days 3, 6 and 10 after the ischemic insult "

Manually curated Databases

No curated data.