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

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dc.contributor.advisor Ki A. Goosens. en_US Saenz, Christopher M en_US
dc.contributor.other Massachusetts Institute of Technology. Dept. of Brain and Cognitive Sciences. en_US 2012-04-26T18:48:42Z 2012-04-26T18:48:42Z 2012 en_US 2012 en_US
dc.description Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2012. en_US
dc.description Cataloged from PDF version of thesis. en_US
dc.description Includes bibliographical references (p. 37-42). en_US
dc.description.abstract 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. en_US
dc.description.statementofresponsibility by Christopher M. Saenz. en_US
dc.format.extent 42 p. en_US
dc.language.iso eng en_US
dc.publisher Massachusetts Institute of Technology en_US
dc.rights 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. en_US
dc.rights.uri en_US
dc.subject Brain and Cognitive Sciences. en_US
dc.title Viral delivery of recombinant growth hormone to rescue effects of chronic stress on hippocampal learning en_US
dc.title.alternative Viral delivery of recombinant GH to rescue effects of chronic stress on HIP learning en_US
dc.type Thesis en_US S.M. en_US
dc.contributor.department Massachusetts Institute of Technology. Dept. of Brain and Cognitive Sciences. en_US
dc.identifier.oclc 783792887 en_US

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