1985 — 1987 |
Vernadakis, Antonia O |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Effects of Opiates During Embryogenesis and Neurogenesis @ University of Colorado Denver
We propose to investigate the direct actions of the narcotic drug LAAM and its two primary metabolites, N-LAAM and DN-LAAM on brain growth in vivo and in culture. The chick embryo will be the experimental animal for the in vivo studies and dissociated brain cell cultures from chick embryos will be the culture system. Specific studies will include: 1. Accumulation and disappearance of 14C-LAAM and its two metabolites in several brain areas of the chick embryo after injection in vivo. 2. The effects of LAAM, N-LAAM and DN-LAAM given at various doses and at various embryonic ages on the development of enzymes associated with growth; ornithine decarboxylase, choline acetyltransferase and tyrosine hydroxylase. 3. The ontological development of opiate receptor binding in several brain areas of the chick and the effects of these narcotic drugs. Using the dissociated brain cell cultures, we will investigate the direct effects of LAAM, N-LAAM and DN-LAAM on morphological growth (neuronal-glial ratio, number and length of neuronal processes, specific neurons affected) and on the maturational profiles of growth enzymes.
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0.934 |
1989 — 1992 |
Vernadakis, Antonia O |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Alcohol Effect in Neuroembryogenesis--in Ovo and Culture @ University of Colorado Denver
neurons; neurogenesis; ethanol; alcoholic beverage consumption; choline acetyltransferase; drug receptors; fetal alcohol syndrome; growth hormone releasing hormone; tyrosine 3 monooxygenase; neurotrophic factors; gene expression; molecular site; teratogens; glutamate decarboxylase; early embryonic stage; enzyme mechanism; epidermal growth factor; developmental neurobiology; organ culture; radioimmunoassay; immunochemistry; fluorescence spectrometry; chick embryo; brain; fluorimetry; radionuclides;
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0.934 |
1990 |
Vernadakis, Antonia O |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Alc Effects in Neuroembryogenesis: in Culture Studies @ University of Colorado Denver |
0.934 |
1992 — 1993 |
Vernadakis, Antonia O |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Alcohol Effect in Neuroembryogenesis-in Ovo &in Culture @ University of Colorado Denver
in our original grant proposal we tested and verified the hypothesis that ethanol administered in ovo early in neuroembryogenesis or given in culture produced severe neuronotoxic effects, affecting differentially the cholinergic, GABAergic and catecholaminergic neuronal phenotypes. Furthermore, we demonstrated that growth factors, NGF, EGF, GHRH and SRIF given concomitantly with ethanol prevent or reverse these early neurotoxic effects. In this competing renewal application we will continue to use the chick embryo and neuron-enriched cultures either each system alone or in an in ovo/in vitro paradigm to further examine and identify more precisely cellular and molecular components involved in ethanol neuronotoxicity and the interaction of ethanol with growth factors. We propose the following studies: a) We will continue our current studies examining the effects of ethanol on growth factor binding sites and also the levels of mRNA encoding NGF, GHRH and SRIF, b) We will identify the survival of specific neuronal populations (cholinergic, GABAergic, catecholaminergic) after ethanol insult using the in ovo/in vitro paradigm and combination of immunocytochemistry and autoradiography. Similarly, we will test the effects of ethanol on cell migration using a combination of immunocytochemistry and autoradiography and we will examine neural cell adhesion by determining the level of NCAM expression during embryonic development. c) To test the hypothesis that ethanol shifts neuronal phenotypic expression we will examine in early embryos the levels of mRNA encoding TH, CHAT, and GAD proteins. d) To test the effects of ethanol on neuronal maturation we will examine in the in vivo/in vitro paradigm the activity df cAMP-dependent protein kinase as one transduction signal important for cell differentiation. With the recent advances in Fetal therapy, we hope that our studies will provide some basic clues of possible therapy and prevention of the Fetal Alcohol Syndrome.
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0.934 |
1994 — 1995 |
Vernadakis, Antonia O |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Alcohol Effect in Neuroembryogenesis in Ovo &in Culture @ University of Colorado Denver
in our original grant proposal we tested and verified the hypothesis that ethanol administered in ovo early in neuroembryogenesis or given in culture produced severe neuronotoxic effects, affecting differentially the cholinergic, GABAergic and catecholaminergic neuronal phenotypes. Furthermore, we demonstrated that growth factors, NGF, EGF, GHRH and SRIF given concomitantly with ethanol prevent or reverse these early neurotoxic effects. In this competing renewal application we will continue to use the chick embryo and neuron-enriched cultures either each system alone or in an in ovo/in vitro paradigm to further examine and identify more precisely cellular and molecular components involved in ethanol neuronotoxicity and the interaction of ethanol with growth factors. We propose the following studies: a) We will continue our current studies examining the effects of ethanol on growth factor binding sites and also the levels of mRNA encoding NGF, GHRH and SRIF, b) We will identify the survival of specific neuronal populations (cholinergic, GABAergic, catecholaminergic) after ethanol insult using the in ovo/in vitro paradigm and combination of immunocytochemistry and autoradiography. Similarly, we will test the effects of ethanol on cell migration using a combination of immunocytochemistry and autoradiography and we will examine neural cell adhesion by determining the level of NCAM expression during embryonic development. c) To test the hypothesis that ethanol shifts neuronal phenotypic expression we will examine in early embryos the levels of mRNA encoding TH, CHAT, and GAD proteins. d) To test the effects of ethanol on neuronal maturation we will examine in the in vivo/in vitro paradigm the activity df cAMP-dependent protein kinase as one transduction signal important for cell differentiation. With the recent advances in Fetal therapy, we hope that our studies will provide some basic clues of possible therapy and prevention of the Fetal Alcohol Syndrome.
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0.934 |