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Molecular correlates of chronic corticosterone exposure in the hippocampus / Suresh Mohanchandran Nair.

LIBRA Thesis N158 1996
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LIBRA Diss. POPM1996.378
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LIBRA microfilm P38:1996
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Format:
Book
Manuscript
Microformat
Thesis/Dissertation
Author/Creator:
Nair, Suresh Mohanchandran.
Contributor:
Eberwine, James H., advisor.
University of Pennsylvania.
Language:
English
Subjects (All):
Penn dissertations--Pharmacology.
Pharmacology--Penn dissertations.
Academic Dissertations as Topic.
Medical Subjects:
Academic Dissertations as Topic.
Local Subjects:
Penn dissertations--Pharmacology.
Pharmacology--Penn dissertations.
Physical Description:
xi, 167 pages : illustrations ; 29 cm
Production:
1996.
Summary:
Corticosterone (CORT) binds to mineralocorticoid (MRs) and glucocorticoid receptors (GRs) in CA1 and CA3 hippocampal neurons, which respond to a wide range of CORT concentrations. Ligand-bound corticosteroid receptors regulate gene expression and alter levels of multiple mRNAs and proteins, thereby influencing basic neuronal properties e.g. membrane potential and Ca-influx. Exposure to high doses of CORT appears to be harmful to neuronal integrity.
Initially, we employed in-situ transcription followed by antisense RNA amplification to characterize CORT-mediated regulation of gene expression in hippocampal sub-regions. Over 4 weeks, no alterations in expression levels of MR or GR mRNAs were seen in the CA1 or CA3. Expression of GLUT-3 mRNA was suppressed in both areas, suggesting a molecular mechanism for inhibition of neuronal glucose uptake by CORT. At 3 weeks, the CA3 expressed a two-fold ratio of NR2A:NR2B mRNA, and may consequently exhibit restricted NMDA receptor-mediated Ca-influx relative to the CA1.
Next, voltage-gated Ca currents were recorded and mRNA expression characterized in individual CA1 neurons to identify regulation of Ca channel mRNAs by CORT.
Notes:
Adviser: James H. Eberwine.
Thesis (Ph.D. in Pharmacology) -- University of Pennsylvania, 1996.
Includes bibliographical references.
Local Notes:
University Microfilms order no.: 97-12981.
OCLC:
187469411

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