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BEHAVIORAL, PATHOLOGICAL, AND PROTEOMIC PROFILING OF A NOVEL MOUSE MODEL OF CO-MORBID COMBAT-RELATED MILD TRAUMATIC BRAI...

Permanent Link: http://ncf.sobek.ufl.edu/NCFE004773/00001

Material Information

Title: BEHAVIORAL, PATHOLOGICAL, AND PROTEOMIC PROFILING OF A NOVEL MOUSE MODEL OF CO-MORBID COMBAT-RELATED MILD TRAUMATIC BRAIN INJURY AND POST-TRAUMATIC STRESS DISORDER A PILOT STUDY
Physical Description: Book
Language: English
Creator: Greenberg, Marianne
Publisher: New College of Florida
Place of Publication: Sarasota, Fla.
Creation Date: 2013
Publication Date: 2013

Subjects

Subjects / Keywords: TBI
PTSD
Mouse Model
Proteomics
Pathology
Genre: bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract: Co-morbid mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) has become the signature disorder for returning service members of Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF). The clinical heterogeneity and symptom overlap of the separate and combined forms underscore the need to develop a pre-clinical model that can reveal and discriminate between these individual disorders. This study details the use of a novel experimental paradigm for combined PTSD and mTBI over an acute time course. Anxiety and spatial memory of mice were assessed after a three-week traumatic stress exposure. At two weeks after the last stress exposure, brain hemispheres of all animals were analyzed using proteomic and immunohistochemical approaches. PTSD animals showed a dramatic increase in anxiety-related behaviors, but no memory impairment was measured at any time point, whereas PTSD+mTBI animals showed a slight increase in anxiety and significant memory impairment. Glial fibrillary acidic protein (GFAP) immunoreactivity was elevated in all examined brain regions of PTSD+mTBI animals, but was decreased in the hippocampus of PTSD animals. Microglial proliferation, manifest as Iba-1 immunoreactivity, was present in the frontal cortex, hypothalamus, and CA1-CA3 of hippocampi from both PTSD and PTSD+mTBI animals. Liquid chromatography-mass spectrometry (LC-MS) based proteomics was used to map protein alterations from soluble protein extracts between PTSD and PTSD+mTBI animals. Using dimethyl labeling coupled with mass spectrometry, more than 160 proteins were quantified, and 7 were found to be differentially expressed. These data suggest that this novel stress-related paradigm for PTSD+mTBI partly recapitulates some of the behavioral as well as biochemical changes in humans. As such, this model may serve as a suitable platform to further explore mTBI and PTSD relevant to veterans returning from combat, with the goal of identifying novel therapeutic strategies to abrogate the pathological effects of this complex disorder.
Statement of Responsibility: by Marianne Greenberg
Thesis: Thesis (B.A.) -- New College of Florida, 2013
General Note: Online version not currently available.
Electronic Access: RESTRICTED TO NCF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE
Bibliography: Includes bibliographical references.
Source of Description: This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Local: Faculty Sponsor: Walstrom, Katherine

Record Information

Source Institution: New College of Florida
Holding Location: New College of Florida
Rights Management: Applicable rights reserved.
Classification: local - S.T. 2013 G79
System ID: NCFE004773:00001

Permanent Link: http://ncf.sobek.ufl.edu/NCFE004773/00001

Material Information

Title: BEHAVIORAL, PATHOLOGICAL, AND PROTEOMIC PROFILING OF A NOVEL MOUSE MODEL OF CO-MORBID COMBAT-RELATED MILD TRAUMATIC BRAIN INJURY AND POST-TRAUMATIC STRESS DISORDER A PILOT STUDY
Physical Description: Book
Language: English
Creator: Greenberg, Marianne
Publisher: New College of Florida
Place of Publication: Sarasota, Fla.
Creation Date: 2013
Publication Date: 2013

Subjects

Subjects / Keywords: TBI
PTSD
Mouse Model
Proteomics
Pathology
Genre: bibliography   ( marcgt )
theses   ( marcgt )
government publication (state, provincial, terriorial, dependent)   ( marcgt )
born-digital   ( sobekcm )
Electronic Thesis or Dissertation

Notes

Abstract: Co-morbid mild traumatic brain injury (mTBI) and post-traumatic stress disorder (PTSD) has become the signature disorder for returning service members of Operation Enduring Freedom and Operation Iraqi Freedom (OEF/OIF). The clinical heterogeneity and symptom overlap of the separate and combined forms underscore the need to develop a pre-clinical model that can reveal and discriminate between these individual disorders. This study details the use of a novel experimental paradigm for combined PTSD and mTBI over an acute time course. Anxiety and spatial memory of mice were assessed after a three-week traumatic stress exposure. At two weeks after the last stress exposure, brain hemispheres of all animals were analyzed using proteomic and immunohistochemical approaches. PTSD animals showed a dramatic increase in anxiety-related behaviors, but no memory impairment was measured at any time point, whereas PTSD+mTBI animals showed a slight increase in anxiety and significant memory impairment. Glial fibrillary acidic protein (GFAP) immunoreactivity was elevated in all examined brain regions of PTSD+mTBI animals, but was decreased in the hippocampus of PTSD animals. Microglial proliferation, manifest as Iba-1 immunoreactivity, was present in the frontal cortex, hypothalamus, and CA1-CA3 of hippocampi from both PTSD and PTSD+mTBI animals. Liquid chromatography-mass spectrometry (LC-MS) based proteomics was used to map protein alterations from soluble protein extracts between PTSD and PTSD+mTBI animals. Using dimethyl labeling coupled with mass spectrometry, more than 160 proteins were quantified, and 7 were found to be differentially expressed. These data suggest that this novel stress-related paradigm for PTSD+mTBI partly recapitulates some of the behavioral as well as biochemical changes in humans. As such, this model may serve as a suitable platform to further explore mTBI and PTSD relevant to veterans returning from combat, with the goal of identifying novel therapeutic strategies to abrogate the pathological effects of this complex disorder.
Statement of Responsibility: by Marianne Greenberg
Thesis: Thesis (B.A.) -- New College of Florida, 2013
General Note: Online version not currently available.
Electronic Access: RESTRICTED TO NCF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE
Bibliography: Includes bibliographical references.
Source of Description: This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida Libraries, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.
Local: Faculty Sponsor: Walstrom, Katherine

Record Information

Source Institution: New College of Florida
Holding Location: New College of Florida
Rights Management: Applicable rights reserved.
Classification: local - S.T. 2013 G79
System ID: NCFE004773:00001

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