| dc.contributor |
Lugo, Joaquin N. |
|
| dc.creator |
Holley, Andrew Jacob, 1990- |
|
| dc.date |
2018-09-07T14:00:49Z |
|
| dc.date |
2018-09-07T14:00:49Z |
|
| dc.date |
2018-08 |
|
| dc.date |
2018-06-11 |
|
| dc.date |
August 2018 |
|
| dc.date |
2018-09-07T14:00:49Z |
|
| dc.date.accessioned |
2022-05-18T12:23:10Z |
|
| dc.date.available |
2022-05-18T12:23:10Z |
|
| dc.identifier |
http://hdl.handle.net/2104/10457 |
|
| dc.identifier.uri |
http://localhost:8080/xmlui/handle/CUHPOERS/30933 |
|
| dc.description |
Studies utilizing rodent models of acute seizures have indicated that a single brief seizure impairs retention of spatial and contextual memory. However, the timespan for which a solitary seizure can impact memory or which kinds of memory it can hinder are obscure. Additionally, evidence for a mechanism underlying seizure-induced memory impairment is lacking. Addressing the first question, we induced a seizure and then trained mice in trace fear conditioning, novel object recognition, or the accelerating rotarod and later examined memory at various time points following the seizure. We also examined activity levels and anxiety-like behavior in the open field and elevated plus maze (EPM). We investigated a potential mechanism using western blot analysis to assess PI3K/Akt/mTOR signaling at time points correlated with the memory tests. We also stained brain tissue taken at 24 hours and one week using hematoxylin and eosin (H&E) to examine for gross damage after a seizure. In the open field, we found a reduction in locomotion 24 hours, but not one week after a seizure. Anxiety-like behavior in the EPM was unchanged. Hippocampal trace fear memory was impaired at 24 hours and one week in mice that experienced a seizure one hour prior to training. Moreover, the level of impairment was more prominent during the one week test. In contrast, non-hippocampal learning and memory was unaffected in the NOR and rotarod tasks. Western analysis revealed increased hippocampal phospho-S6 and total FMRP one hour after a seizure. H&E stained tissue revealed no indication of cellular damage or gross lesions. Together our data indicates that a brief seizure selectively impairs hippocampal learning and memory, while sparing non-hippocampal learning and memory. Increased PI3K/Akt/mTOR and altered FMRP signaling one hour after a seizure suggests that changes to de novo protein synthesis necessary for memory consolidation underlie the memory impairments we observed. The lack of overt damage and transient changes in molecular signaling in the current study in comparison to studies using chronic and multiple seizure models suggests a different mechanism underlies memory impairment associated with brief seizure activity. |
|
| dc.format |
application/pdf |
|
| dc.format |
application/pdf |
|
| dc.format |
application/pdf |
|
| dc.language |
en |
|
| dc.rights |
Worldwide access. |
|
| dc.rights |
Access changed 12/14/20. |
|
| dc.subject |
Epilepsy. Synaptic plasticity. Amnesia. |
|
| dc.title |
A brief seizure prior to learning selectively impairs hippocampal learning and memory and is associated with alterations in PI3K/Akt/mTOR and FMRP signaling. |
|
| dc.type |
Thesis |
|
| dc.type |
text |
|