Dissertation Defense: Investigating Sex-Specific Responses in a Preclinical Model of Traumatic Brain Injury: Development of Chronic Depression-Like Behavior and Glutamatergic Protein Changes
Dissertation Defense: Investigating Sex-Specific Responses in a Preclinical Model of Traumatic Brain Injury: Development of Chronic Depression-Like Behavior and Glutamatergic Protein Changes
Caiti-Erin Talty
Graduate Student, Translational Biology, Medicine, and Health
Graduate Research Assistant, VandeVord Lab
November 22, 2024, at 11:30a.m.
Room 2124, Gilbert Hall
About this Dissertation
Concussion is the most common form of brain injury, comprising over 80% of traumatic brain injuries (TBIs) occurring in the United States and around the world. While many individuals are able to fully recover in the weeks following a concussion, an estimated 50% of patients go on to suffer from persistent symptoms that may range from months to years in duration. Among the most common complaints of those with persistent symptoms is sadness or depression, and significantly elevated rates of suicide have been reported in this population. Females are more likely to develop persistent symptoms and have reported higher rates of neuropsychiatric symptoms than males following injury. Altered glutamatergic neurotransmission has been implicated as a possible cause of depression following concussion due to similarities in glutamatergic changes that occur following concussion and during depression, independently of brain injury. Excitotoxicity is known to occur following TBI, resulting in neuronal death, and dysfunction in the cells that survive. Glutamatergic dysfunction occurring in regions such as the hippocampus, prefrontal cortex or amygdala, may be a driver of depressed mood or major depressive disorder (MDD) in concussed individuals as these regions, among others, have previously been linked to MDD. There are currently no approved pharmacological treatments for TBI symptoms. Therefore, gaining insight into chronic pathophysiology underlying TBI symptoms, including depression, is essential to support the development of therapeutic approaches for patients.
The glutamate system represents a promising avenue of investigation in the context of chronic TBI pathophysiology. Using a clinically-relevant rodent model of concussion, this work sought to elucidate chronic glutamatergic changes occurring in the brain in association with the development of depression-like behavior following injury. Delayed-onset deficits in social and self-care behaviors were observed in association with region-specific changes in N-methyl-D-aspartate (NMDA) receptor and glutamate transporter expression in injured male animals. Females responded differently to injury, showing disinhibition and compulsive behaviors in conjunction with upregulation in glutamatergic signaling proteins. Further, this work aimed to investigate chronic sex-specific responses to TBI. Direct comparisons of behavioral changes in injured males and females demonstrated differences in both the emergence and nature of behavioral deficits. Examinations of hippocampal subregions showed deeper specificity in expressional changes in glutamatergic markers with both region- and sex-specific alterations observed at a chronic time point. Additionally, proteomic analysis was employed to evaluate widespread protein-level changes in the injured frontal cortex, and results revealed significant dysregulation in pathways involved in excitatory neurotransmission and calcium signaling. However, the dysregulated proteins within these pathways differed in a sex-dependent manner, indicating a sexual dimorphism in chronic TBI pathophysiology. Potential drug targets were also identified for investigation in future studies. The fundamental work presented in these studies provides strong evidence of dynamic, sex-specific modifications in the glutamate system in association with chronic TBI deficits in a translational model, ultimately providing a foundation for future development of therapeutic options to improve the lives of patients suffering with persistent symptoms.
More About the Candidate and Project
- Education and Training
- Committee Members
- Publications and Presentations
- Honors and Awards and Service
Education
Virginia Tech, Translational Biology, Medicine, and Health, Ph.D. Candidate
Binghamton University, B.S. Integrative Neuroscience
Training
Graduate Research Assistant, VandeVord Lab
Mentor
Pamela VandeVord, Ph.D., Professor, Biomedical Engineering and Mechanics
Committee Members
- Georgia Hodes, Ph.D., Professor, Human Nutrition, Foods, and Exercise
- Sharon Swanger, Ph.D., Assistant Professor, School of Neuroscience
- Pearl Chiu, Ph.D., Professor, Fralin Biomedical Research Institute at VTC
- Blaise Costa, MPharm, Ph.D., Professor, VCOM
Publications
Talty, C. E., Murphy, S., & VandeVord, P. (2024). Mild traumatic brain injury gives rise to chronic depression-like behavior and associated alterations in glutamatergic protein expression. Neuroscience, 560, 198-210.
Talty, C. E., Murphy, S., Desai, S., & VandeVord, P. (2024). Manifestation of chronic depression-like behavior and glutamatergic signaling alterations in female rats following traumatic brain injury. Journal of Neurotrauma.
Norris, C., Murphy, S. F., Talty, C.-E., & Vandevord, P. J. (2024). Spatial intracranial pressure fields driven by blast overpressure in rats. Annals of Biomedical Engineering, 1-14.
Talty, C.-E., Murphy, S., & VandeVord, P. (2024). Closed-head controlled impact model in adult rats- VandeVord Lab. protocols.io.
Talty, C. E., Murphy, S., & VandeVord, P. (2023). The development of chronic depression-like behavior following closed-head impact traumatic brain injury. IBRO Neuroscience Reports, 15, S206-S207.
Talty, C.-E., Norris, C., & VandeVord, P. (2022). Defining experimental variability in actuator-driven closed head impact in rats. Annals of Biomedical Engineering, 50(10), 1187-1202.
Talty, C. E., Dickerson, M., & VandeVord, P. (2022). Dysfunctional glutamatergic neurotransmission in a preclinical model of concussion. Journal of Neurotrauma, 39(11-12), A39-A40.
Presentations
Talty C.-E. (2024, June). Turning your paper into a paper of the future [Oral presentation]. National Neurotrauma Society Symposium, San Francisco, CA, USA.
Talty C.-E., Murphy, S., Desai, S. & VandeVord, P. (2024, June). Manifestation of chronic depression-like behavior and glutamatergic signaling alterations in female rats following traumatic brain injury [Poster presentation]. National Neurotrauma Society Symposium, San Francisco, CA, USA.
Talty C.-E., Murphy, S., & VandeVord, P. (2023, December). Emergence of chronic depression-like behavior and changes in N-methyl-D-aspartate receptor expression following closed-head impact traumatic brain injury [Poster presentation]. Translational Biology, Medicine & Health Research Symposium, Roanoke, VA, USA.
Talty C.-E., Murphy, S., & VandeVord, P. (2023, November). Emergence of chronic depression-like behavior and changes in N-methyl-D-aspartate receptor expression following closed-head impact traumatic brain injury [Poster presentation]. Neuroscience 2023, Washington, DC, USA.
Talty C.-E., Murphy, S., & VandeVord, P. (2023, September). The development of chronic depression-like behavior following closed-head impact traumatic brain injury [Poster presentation]. 11th International Brain Research Organization World Congress, Granada, Spain.
Talty C.-E., Murphy, S., & VandeVord, P. (2023, January). Evaluating chronic depressive-like behavior following single and repeated closed-head impact [Poster presentation]. Translational Biology, Medicine & Health Research Symposium, Roanoke, VA, USA.
Talty C.-E., Dickerson, M., & VandeVord, P. (2022, June). Dysfunctional glutamatergic neurotransmission in a preclinical model of concussion [Poster presentation]. National Neurotrauma Society Symposium, Atlanta, GA, USA.
Murphy, S., Dickerson, M., Talty, C.-E., Brolinson, G., & VandeVord, P. (2022, March). Osteopathy in the cranial field as a method to enhance brain injury recovery: a preliminary study [Oral presentation]. American Academy of Osteopathy & American Osteopathic Academy of Sports Medicine Convocation, Orlando, FL, USA.
Talty C.-E., Dickerson, M., & VandeVord, P. (2022, February). Changes in glutamatergic neurotransmission following impact traumatic brain injury [Poster presentation]. Edward Via College of Osteopathic Medicine Virginia Research Recognition Day, Blacksburg, VA, USA.
Talty, C.-E., Strickler, J., & VandeVord, P. (2021, April). Effects of acute stress paradigm on glial activation and DNA methylation: a pilot study [Oral presentation]. Translational Biology, Medicine & Health Program Rotation Oral Presentation Symposium, Blacksburg, VA, USA.
Talty, C.-E., Brolinson, G., Murphy, S., & VandeVord, P. (2021, March). Osteopathic treatment effects on blood-brain barrier integrity following blast traumatic brain injury [Poster presentation]. Translational Biology, Medicine & Health Program Rotation Poster Presentation, Blacksburg, VA, USA.
Talty, C.-E., Goetz, A., Lepore, J., Rundquist, L., & Zeng, S. (2018, December). Effects of varying isoflurane anesthesia levels on serotonin and dopamine concentrations in the rat motor circuit [Poster presentation]. First-Year Research Immersion Program Annual Symposium, Vestal, NY, USA.
Talty, C.-E., Gerisma, J., Howard, J., Lerner, K., & Russo, J. (2017, December). Comparing and contrasting models of akinesia in 6-OHDA lesioned rats [Poster presentation]. First-Year Research Immersion Program Annual Symposium, Vestal, NY, USA.
Honors and Awards
Graduate and Professional Student Senate Travel Fund Program Grant Recipient Fall 2023 ($300)
Graduate Research Development Program Grant Recipient Spring 2023 ($850)
1st Place Research Podium Presentation at AAO & AOASM Convocation 2022 (co-author)
“Most Creative” Award at HS&T Hokie Pitch 2020 ($1000)
Service
STEM Professional, Letters to a Pre-Scientist August 2023 – Present
Ambassador, Translational Biology, Medicine & Health Program August 2023 – Present
Peer Mentor, Translational Biology, Medicine & Health Program May 2021 – Present