Viral delivery of recombinant growth hormone to rescue effects of chronic stress on hippocampal learning

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012.

Bibliographic Details
Main Author: Saenz, Christopher M
Other Authors: Ki A. Goosens.
Format: Thesis
Language:eng
Published: Massachusetts Institute of Technology 2012
Subjects:
Online Access:http://hdl.handle.net/1721.1/70385
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author Saenz, Christopher M
author2 Ki A. Goosens.
author_facet Ki A. Goosens.
Saenz, Christopher M
author_sort Saenz, Christopher M
collection MIT
description Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012.
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spelling mit-1721.1/703852019-04-08T08:00:49Z Viral delivery of recombinant growth hormone to rescue effects of chronic stress on hippocampal learning Viral delivery of recombinant GH to rescue effects of chronic stress on HIP learning Saenz, Christopher M Ki A. Goosens. Massachusetts Institute of Technology. Dept. of Brain and Cognitive Sciences. Massachusetts Institute of Technology. Dept. of Brain and Cognitive Sciences. Brain and Cognitive Sciences. Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012. Cataloged from PDF version of thesis. Includes bibliographical references (p. 37-42). Chronic stress has been linked to variation in gene regulation in the hippocampus (HIP) among other areas. These lead to cytoskeletal and volumetric rearrangements in various nuclei of the central nervous system and are thought to contribute to several stress-sensitive disorders. One such gene that has been shown to be downregulated in HIP in response to stress is somatotropin, colloquially known as growth hormone (GH). These experiments were conducted to develop a novel assay for examination of working memory in rats and explore the nature of stress-induced impairment of hippocampal function and determine whether infusion of a modified herpes simplex virus (HSV) carrying the recombinant rodent growth hormone (GH) would be sufficient to restore normal hippocampal function. After 21 days of chronic immobilization stress (CIS), animals received bilateral infusions into the dorsal HIP of 2[mu]l HSV carrying either GH with green florescent protein (GFP) or GFP only. On the second day following the infusion, the animals received trace conditioning, a HIP-dependent task, with five tone-shock pairings of a 16 second tone followed by a 30 second trace interval terminating with a 1 second 0.85 milliamp footshock. An inter-trial interval of 3 minutes was used to separate the tone-shock pairings. The following day the animals were tested for fear to the context and for fear to the tone in a novel context, measured by amount of time the animal spent freezing. Using this criterion, animals that had undergone stress that received the control vector were less likely to freeze when presented with the tone, indicating an impairment of hippocampal function. Viral-mediated overexpression of GH in the dorsal HIP was able to reverse the CIS-related impairment in hippocampal function. ELISA was used to verify the expression of GH from the infused vector. These experiments may yield future directions of investigation for stress-based disorders. by Christopher M. Saenz. S.M. 2012-04-26T18:48:42Z 2012-04-26T18:48:42Z 2012 2012 Thesis http://hdl.handle.net/1721.1/70385 783792887 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 42 p. application/pdf Massachusetts Institute of Technology
spellingShingle Brain and Cognitive Sciences.
Saenz, Christopher M
Viral delivery of recombinant growth hormone to rescue effects of chronic stress on hippocampal learning
title Viral delivery of recombinant growth hormone to rescue effects of chronic stress on hippocampal learning
title_full Viral delivery of recombinant growth hormone to rescue effects of chronic stress on hippocampal learning
title_fullStr Viral delivery of recombinant growth hormone to rescue effects of chronic stress on hippocampal learning
title_full_unstemmed Viral delivery of recombinant growth hormone to rescue effects of chronic stress on hippocampal learning
title_short Viral delivery of recombinant growth hormone to rescue effects of chronic stress on hippocampal learning
title_sort viral delivery of recombinant growth hormone to rescue effects of chronic stress on hippocampal learning
topic Brain and Cognitive Sciences.
url http://hdl.handle.net/1721.1/70385
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