The effects of ethanol exposure on glial derived neurotrophic factor-mediated trophic support /
Ethanol consumption during fetal development can lead to a constellation of behavioral and anatomical defects collectively termed fetal alcohol syndrome or FAS (Jones and Smith, 19939 Jones et a1., 1973).[] The present studies were designed to determine whether glial derived neurotrophic factor (GDN...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
1999.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=733674521&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | Ethanol consumption during fetal development can lead to a constellation of behavioral and anatomical defects collectively termed fetal alcohol syndrome or FAS (Jones and Smith, 19939 Jones et a1., 1973).[] The present studies were designed to determine whether glial derived neurotrophic factor (GDNF) could prevent ethanol-induced cerebellar Purkinje cell loss. Ethanol exposure results in Purkinje cell loss in cerebellar explant cultures, and concurrent administration of GDNF can attenuate ethanol-induced Purkinje cell loss. The cerebellum expresses GDNF and the receptors required to provide trophic support for developing Purkinje cells. However, endogenous GDNF does not ameliorate ethanol-induced Purkinje cell loss. These experiments determined that ethanol reduces the amount of GDNF protein released from cerebellar exploit cultures without affecting mRNA expression. Therefore, exogenous GDNF may overcome this loss of endogenous GDNF. In addition, since ethanol exposure decreases GDNF protein levels, additional studies examined whether ethanol disrupts GDNF- mediated signal transduction in a GDNF responsive cell line (SK-N-SH). Ethanol administration selectively activated a mitogen-activated protein (MAP) kinase pathway that is associated with apoptosis (c-Jun NHâ‚‚- terminal protein kinase, JNK) but not a pathway associated with differentiation and proliferation (extracellular signal regulated kinase, ERK). Ethanol administration resulted in a significant increase in necrotic cell death. In addition, ethanol exposure results in DNA fragmentation and phosphatidylserine translocation to the outer leaflet of the plasma membrane, characteristics of apostolic cell death. Concurrent administration of GDNF was able to attenuate ethanol-induced increases in JNK phosphorylation and apoptosis. These findings suggest that exogenous GDNF may play a crucial role in the attenuation of ethanol- induced Purkinje cell death. |
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| Item Description: | Vita. "Major Subject: Medical Science". |
| Physical Description: | xii, 116 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilm Inc. |
| Bibliography: | Includes bibliographical references (leaves 83-109). |