Abstract
The role of apoptotic signaling proteins for long-lived neurons in the mature brain is poorly understood. Recently, we have shown that water deprivation leads to the activation of vasopressin (VP) secretion and expression of Bcl-2 and caspase-9 apototic proteins in the hypothalamus of the rat brain. In the present work, we continued to study a possible relationship between the functional activity of neurosecretory cells of the hypothalamus and apoptosis related proteins. We found that water deprivation leads to simultaneous activation of synthesis of VP and p53 and Bcl-2 apoptotic proteins in the mouse brain. To study a possible effect of apoptotic proteins on the functional state of hypothalamic neurons, the VP and tyrosine hydroxylase (TH) synthesis were analyzed in p53, p21Waf1/Cip1 and Bcl-2 deficient mice. Loss of p53 and Bcl-2 significantly reduced VP synthesis in paraventricular and supraoptic nuclei and TH expression in arcuat, periventricular and zona incerta nuclei of the hypothalamus. Surprisingly, in contrast with the loss of p53, the inactivation of p21Waf1/Cip1 up-regulates the expression of VP and TH. These data indicate that p53, p21Waf1/Cip1 and Bcl-2 proteins, besides affecting cell cycle, tumor suppression and apoptosis, may act as modulators of neurosecretory activity of hypothalamic neurons; however, this problem remains to be determined more detailed.
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Acknowledgments
We gratefully acknowledge P. Leder and M Sentner for p21Cip1/Waf1 and bcl-2 deficient mice, respectively. We also thank H. Gainer for the vasopressin expressing vector and S. Gambaryan for advices during in situ experiments. We are grateful to A. Kretz and S. Hollis for the critical reading of manuscript and stimulation of helpful discussion. The study was supported in part by Russian Foundation for Fundamental Research (Grants RFBR 01-04-48825 and RFBR 05-04-48099-a) and German Program Neue Bundesland (NBL-3).
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Chernigovskaya, E.V., Taranukhin, A.G., Glazova, M.V. et al. Apoptotic signaling proteins: possible participation in the regulation of vasopressin and catecholamines biosynthesis in the hypothalamus. Histochem Cell Biol 124, 523–533 (2005). https://doi.org/10.1007/s00418-005-0016-x
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DOI: https://doi.org/10.1007/s00418-005-0016-x