The Role of p53 in the Proliferation and Differentiation of Neural Stem Cells in Organotypic Cultures of Mouse Hippocampus

Autor: Margarita Glazova, Yu. S. Grigor’eva
Rok vydání: 2015
Předmět:
Zdroj: Neuroscience and Behavioral Physiology. 45:627-636
ISSN: 1573-899X
0097-0549
Popis: We report here our studies of the effects of p53 on the proliferation and differentiation of neural stem cells (NSC) in organotypic hippocampal cultures from adult mice. The role of p53 was assessed experimentally by using the p53 inhibitor pifi thrin-alpha (PFT) and the p53 activator tenovin-1 (TEN). The results show that administration of PFT had no effect on the number of phosphohistone H3-immunopositive cells in the subgranular zone of the hippocampus. This is evidence that inhibition of p53 did not alter the level of NSC proliferation. Administration of TEN, conversely, increased the proliferative activity of NSC. Analysis of Pim-1 and Phb1 proteins, which are involved in regulating the cell cycle, showed that activation of p53, which activated proliferation, also increased the Pim-1 level. These results are consistent with published data and provide evidence that Pim-1 positively regulates the cell cycle in NSC. In contract to Pim-1, Phb1 had antiproliferative activity. Our results indicated that TEN inhibits Phb1 expression. Administration of PFT initially led to an increase in the Phb1 level, which was followed by a sharp drop, with no change in the level of proliferation. Thus, the increase in the level of proliferation seen here in response to administration of TEN was partially dependent on inhibition of the antiproliferative function of Phb1. These studies demonstrate that both TEN and, to a greater extent, PFT stimulated neuronal differentiation, activating CRMP-2 expression, but had no effect on gliogenesis. These results show that p53 is an important factor in the regulation of neuronal differentiation, which is probably mediated by proteins associated with cell cycle regulation, such as Pim-1 and Phb1.
Databáze: OpenAIRE
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