Virginia Tech
Aberrant hippocampal neurogenesis contributes to learning and memory deficits in a mouse model of repetitive mild traumatic brain injury
Abstract
dc:description.abstractAdult hippocampal neurogenesis, or the process of creating new neurons in the dentate gyrus (DG) of the hippocampus, underlies learning and memory capacity. This cognitive ability is essential for humans to operate in their everyday lives, but cognitive disruption can occur in response to traumatic insult such as brain injury. Previous findings in rodent models have characterized the effect of moderate traumatic brain injury (TBI) on neurogenesis and found learning and memory shortfalls correlated with limited neurogenic capacity. While there are no substantial changes after one mild TBI, research has yet to determine if neurogenesis contributes to the worsened cognitive outcomes of repetitive mild TBI. Here, we examined the effect of neurogenesis on cognitive decline following repetitive mild TBI by utilizing AraC to limit the neurogenic capacity of the DG. Utilizing a BrdU fate-labeling strategy, we found a significant increase in the number of immature neurons that correlate learning and memory impairment. These changes were attenuated in AraC-treated animals. We further identified endothelial cell (EC)-specific EphA4 receptor as a key mediator of aberrant neurogenesis. Taken together, we conclude that increased aberrant neurogenesis contributes to learning and memory deficits after repetitive mild TBI.
Degree
thesis:*- Name thesis:degree_name
- Doctor of Philosophy
- Level thesis:degree_level
- doctoral
- Discipline thesis:degree_discipline
- Translational Biology, Medicine and Health
- Department dc:contributor.department
- Graduate School
- Grantor dc:publisher
- Virginia Tech
- Year dc:date.issued
- 2019
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Greer, Kisha
- Chair dc:contributor.committeechair
-
- Theus, Michelle H.
- Committee members dc:contributor.committeemember
-
- Gourdie, Robert G.
- He, Jia-Qiang
- Eyestone, Willard H.
- Chappell, John C.
Subjects
dc:subject × 5Rights
dc:rights- Statement dc:rights
-
- In Copyright
- Licence dc:rights.uri
Identifiers
dc:identifier.*- Dc Identifier Other
- vt_gsexam:22121
- OAI identifier oai:identifier
- oai:vtechworks.lib.vt.edu:10919/94329