Pharmacological Stimulation or Suppression of Neurogenesis

For the experiments to increase in postnatal neurogenesis, memantine (MEM) at a dose of 10 mg/kg which has been found to enhance the proliferation of radial glia-like progenitor cells (Sun et al., 2015) was applied to increase the neurogenesis in hippocampal dentate gyrus. Memantine which purchased from Sigma (M9292) was dissolved in sterile 0.9% saline solution to yield a final concentration of 1 mg/ml. And then the animals received memantine treatment (10 mg/kg) through intraperitoneal injection every 2 days for a period of 2 weeks before behavioral analyses. For the experiments to temporal suppress postnatal neurogenesis, temozolomide (TMZ) was used to block the active cell division of neural stem cells. Temozolomide (T2577) which purchased from Sigma was dissolved in sterile 0.9% saline solution to yield a final concentration of 2.5 mg/ml. The animals with temozolomide treatment received a procedure of 2-week intraperitoneal injections of TMZ which composed of 25 mg/kg TMZ injection once a day for three consecutive days followed by 4 days of non-injection recovery. Such injection regimen was adapted from the glioma treatment in clinic and has been shown to reduce neurogenesis in mice effectively (Garthe et al., 2009). Two cycles of TMZ injection was applied for the TMZ treatment group of animals, whereas the vehicle group received injection of saline solution only.