The proposed studies will explore the ontogeny of fetal central osmotic-dipsogenic mechanisms to develop an understanding of normal and abnormal fluid homeostatic responses. The investigators hypothesize: a) osmotic-dipsogenic responsiveness develops as a result of maturation of neural pathways integrating the subfornical organ (sSFO) and organum vasculosum of the lamina terminalis (OVLT) with the median preoptic nucleus (MnPO). b) The development of endocrine modulation of dipsogenic responses coincides with the onset of specific receptor binding in the SFO, OVLT, and MnPO. And c) Fetal dipsogenic responses to hyperosmolarity may be fundamentally different from the adult, as a result of the developmental pattern of dipsogenic mechanisms. A stepwise series of experiments is proposed: 1) The ontogeny of the responsiveness of putative osmotic dipsogenic central nuclei (SFO, OVLT, MnPO) will be examined with neuronal activation (cFos) staining and nuclei miroinjections; 2) The essential role of these nuclei will be investigated via nuclei microablation; 3) The development of interconnecting dipsogenic neuronal pathways will be investigated with neural tract tracing techniques; and 4) The maturation of the endocrine modulation of dipsogenic responses will be correlated with changes in cerebral endocrine receptor binding and immunochemical staining.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK043311-07
Application #
2701094
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Hamilton, Frank A
Project Start
1991-08-01
Project End
2003-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
7
Fiscal Year
1998
Total Cost
Indirect Cost
City
Torrance
State
CA
Country
United States
Zip Code
90502
Desai, Mina; Gayle, Dave A; Casillas, Ederlen et al. (2009) Early undernutrition attenuates the inflammatory response in adult rat offspring. J Matern Fetal Neonatal Med 22:571-5
Ross, Michael G; Beall, Marie H (2008) Adult sequelae of intrauterine growth restriction. Semin Perinatol 32:213-8
Mansano, Roy; Desai, Mina; Garg, Ambica et al. (2007) Enhanced nephrogenesis in offspring of water-restricted rat dams. Am J Obstet Gynecol 196:480.e1-6
Ross, Michael G; Desai, Mina; Khorram, Omid et al. (2007) Gestational programming of offspring obesity: a potential contributor to Alzheimer's disease. Curr Alzheimer Res 4:213-7
Gayle, Dave A; Desai, Mina; Casillas, Ederlen et al. (2006) Gender-specific orexigenic and anorexigenic mechanisms in rats. Life Sci 79:1531-6
El-Haddad, Mostafa A; Chao, Conrad R; Ross, Michael G (2005) N-methyl-D-aspartate glutamate receptor mediates spontaneous and angiotensin II-stimulated ovine fetal swallowing. J Soc Gynecol Investig 12:504-9
El-Haddad, Mostafa A; Ismail, Yaser; Gayle, Dave et al. (2005) Central angiotensin II AT1 receptors mediate fetal swallowing and pressor responses in the near-term ovine fetus. Am J Physiol Regul Integr Comp Physiol 288:R1014-20
Ross, Michael G; Desai, Mina (2005) Gestational programming: population survival effects of drought and famine during pregnancy. Am J Physiol Regul Integr Comp Physiol 288:R25-33
El-Haddad, Mostafa A; Jia, Yousheng; Ross, Michael G (2005) Persistent sucrose stimulation of ovine fetal ingestion: lack of adaptation responses. J Matern Fetal Neonatal Med 18:123-7
Beall, Marie H; El Haddad, Mostafa; Gayle, Dave et al. (2004) Adult obesity as a consequence of in utero programming. Clin Obstet Gynecol 47:957-66; discussion 980-1

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