Date of Award
Joan C. Edwards School of Medicine
Type of Degree
Lawrence M. Grover
Todd L. Green
William D. McCumbee
Long term potentiation (LTP) in the hippocampus is considered a cellular basis of learning memory. Sleep deprivation, especially rapid eye movement (REM) sleep deprivation, impairs learning and memory as well as LTP. Since most of the previous LTP studies were conducted in the in vitro condition, the full consequences of sleep deprivation (SD) in the living animal are yet to be found. Thus, I tested hippocampal LTP in living animals after 5 days of REM sleep deprivation to determine the effect of SD in vivo. SD also disrupts growth hormone (GH) release. Recent evidence indicates that GH regulates cognitive and hippocampal synaptic function. However, the relationship between GH and synaptic function during SD is not well established. Since the N-methyl-D- aspartate receptor (NMDAR) has an important role in inducing LTP, I hypothesized that loss of normal GH signals during SD would impair synaptic NMDAR expression and function, and treating SD animals with GH would restore normal NMDAR expression and function. To test my hypothesis, I treated animals with GH during 3 days of SD, and tested NMDAR dependent hippocampal synaptic functions and measured synaptic expression of NMDAR subunits. In addition, I measured corticosterone concentration in control and sleep deprived animals to determine stress levels in each treatment. My results showed that LTP in vivo was impaired after 5 days of SD. NMDAR function was impaired and there was a selective loss of NR2B NMDAR subunits from synaptic membranes. These changes in NMDAR function and expression can explain the LTP impairment caused by SD. In agreement with my hypothesis, the LTP and NMDAR impairments were reversed by GH treatment during SD. Finally, there was no difference in corticosterone concentration between control and SD animals, demonstrating that differences in stress were not responsible for any of the changes I observed during SD.
Somatotropin (Growth hormone).
Kim, Eun Young, "Effect of Growth Hormone on Hippocampal Synaptic Function during Sleep Deprivation" (2009). Theses, Dissertations and Capstones. 689.