Pharmaceutical and Natural (Exercise) Mechanisms to Mitigate the Negative Impact of PTSD and Chronic Stress on Synaptic Plasticity and Memory
Synapses can be altered due to experiences in a process called synaptic plasticity, which causes memory formations. Synapses can be strengthened through methods known as long-term potentiation (LTP) or weakened through long-term depression (LTD). Stresses can cause changes by altering synapses through either LTP or LTD. Rats were used to study the effects of post-traumatic stress disorder (PTSD)-like symptoms and a prophylactic treatment using pharmaceuticals. The first model used was the single prolonged stress (SPS) with two weeks of chronic light, which was not as effective for causing changes in synaptic plasticity. The second model, seven days of social defeat (SD) with two weeks of chronic light was more effective at inducing PTSD-like behavior symptoms and causing changes in LTP levels in the ventral hippocampus, amygdala, and prefrontal cortex between stressed and non-stressed rats. For the prophylactic treatment, propranolol and mifepristone were administered one week prior to and throughout the two weeks of the social defeat protocol. The drugs were able to prevent the changes due to stress on LTP in the three aforementioned brain regions, but did not change the anxious behavior of the rats. An enzyme-linked immunosorbent assay (ELISA) was used to determine corticosterone and norepinephrine levels between the different groups of rats. No significant differences were detected between SD and control rats, but SD injected rats were different from controls indicating that the injections were causing added stress. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was used to detect changes in the adrenergic, corticoid, AMPA, and NMDA receptors. There were a few significant changes to some of the targets indicating that the stress protocol and drugs were having an effect on the mRNA expression. Propranolol and mifepristone could possibly be used as a prophylactic treatment for traumatic stress. In a separate study, techniques were used to determine the negative effects chronic stress (non-PTSD-like) has on synaptic plasticity in the dorsal hippocampus and to show how exercise was able to mitigate some of those negative stress effects. Electrophysiology showed differences in LTP between four groups of mice: sedentary no stress (SNS), sedentary with stress (SWS), exercise with stress (EWS), and exercise no stress (ENS). SWS had the lowest amount of LTP, whereas ENS had the highest. SNS and EWS had similar levels of LTP, which were in between the SWS and ENS groups. Corticosterone blood levels measured by an ELISA showed significant increases in the stressed groups compared to the non-stressed groups. The radial arm maze showed that both groups of exercise mice made fewer reference memory errors the second week of testing compared to the sedentary groups. RT-qPCR determined that brain-derived neurotrophic factor (BDNF) and corticoid and dopamine 5 receptors were likely causing some of the memory changes.
College and Department
Life Sciences; Physiology and Developmental Biology
BYU ScholarsArchive Citation
Miller, Roxanne M., "Pharmaceutical and Natural (Exercise) Mechanisms to Mitigate the Negative Impact of PTSD and Chronic Stress on Synaptic Plasticity and Memory" (2017). Theses and Dissertations. 7294.
chronic stress, LTP, LTD, corticoid receptor, dopamine receptor, adrenergic receptor, exercise, propranolol, mifepristone, BDNF, hippocampus, amygdala, prefrontal cortex