“
“Regulation of adult hippocampal neurogenesis in mice responds to behavioral stimuli, including physical activity (RUN) and the exposure to enriched environments

(ENR). If studied after days or weeks, these stimuli and the pathological stimulus of kainic acid-induced seizures (KA) show differential effects on different developmental stages of adult neurogenesis. The question thus arose, 4SC-202 whether such differential effects would also be apparent under very acute conditions. To further refine our method for identifying key restriction points in adult neurogenesis we here used the first expression of granule cell-specific transcription factor prospero-related homeobox I (Prox1) to identify lineage-determined progenitor cells in a nestin-green fluorescent protein (GFP) reporter gene mouse and labeled proliferating precursor cells with bromodeoxyuridine (BrdU). Twenty-four hours after the stimulus adult neurogenesis showed a very similar response to the three paradigms, in that cell proliferation increased. Detailed analysis, however, revealed the following new results: (1) KA, but not RUN and ENR stimulated the Givinostat concentration division of radial glia-like type-1 cells, (2) KA led to the disappearance of proliferative undetermined progenitor cells (type-2a), (3) only RUN increased proliferation

of type-2a cells, (4) ENR and KA, in contrast, acted on lineage-determined progenitor cells (type-2b and type-3) even under acute conditions, and (5) only in the case of KA the short-term stimulus resulted in measurably increased survival of newborn neurons 4 weeks later. These results confirm and specify the idea that in the course of neuronal development in the adult hippocampus, precursor cells acutely sense and distinguish various forms of “”activity”" differentially and

translate these stimuli into defined responses based on their stage of development. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.”
“A significant impediment to the success of cancer chemotherapy ABT737 is the occurrence of multidrug resistance, which, in many cases, is attributable to overexpression of membrane transport proteins, such as the 170-kDa P-glycoprotein (P-gp). Also, upregulation of the phosphatidylinositol 3-kinase (PI3K)/Akt-signaling pathway is known to play an important role in drug resistance, and has been implicated in the aggressiveness of a number of different cancers, including T-acute lymphoblastic leukemia (T-ALL). We have investigated the therapeutic potential of the novel Akt inhibitor, perifosine (a synthetic alkylphospholipid), on human T-ALL CEM cells (CEM-R), characterized by both overexpression of P-gp and constitutive upregulation of the PI3K/Akt network. Perifosine treatment induced death by apoptosis in CEM-R cells.