博士 / 國防醫學院 / 生命科學研究所 / 86 / Corticotropin-releasing factor injected into the dentate gyrus of hippocampus produced a dose-dependent and long-lasting enhancement in synaptic efficacy of these neurons, as measured by an increase in the amplitude and slope of population excitatory postsynaptic potentials as well as the amplitude of population spike. The onset of corticotropin-releasing factor-induced potentiation was slow. It was observed approximately 30-50 min after corticotropin-releasing factor administration and lasted for more than 5
hr. This effect of corticotropin-releasing factor was blocked by pretreatment with the cyclase-adenosine-3,5-monophosphate (cAMP) inhibitor Rp-adenosine-3,5-cyclic monophosphothiolate triethylamine (Rp-cAMPS) and partially blocked by the N-methyl-D-aspartate receptor antagonist MK-801. Further, pretreatment with corticotrophin-releasing factor receptor antagonist, (-helical CRF 9-41, dose-dependently diminished tetanization-induced long-term potentiation and that corticotrophin-releasing factor and tetanic s
timuli had an additive effect on hippocampal neuron excitation. If hippocampal neurons were maximally excited with high dose of corticotropin-releasing factor or four trains of tetanic stimulation at the beginning, additional tetanization or corticotropin-releasing factor was without a further excitation effect. Moreover, direct injection of corticotropin-releasing factor increased cAMP level in the dentate gyrus. These results together suggest that corticotropin-releasing factor-induced potentiation simulate
s the late phase of tetanization-induced long-term potentiation and cAMP seems to be the messenger mediating this effect. Moreover, tetanization-induced long-term potentiation increased some CRF mRNA expression, but did not increase CRF release from the dentate gyrus. These results suggest that CRF neurons may be activated during tetanization-induced long-term potentiation and that the perforant pathway did not synapse on CRF terminals directly. Corticotropin-releasing factor-induced potentiation and long-ter
m potentiation may share some similar mechanisms and corticotropin-releasing factor is probably involved in the neural circuits underlying long-term potentiation. Thus, corticotropin-releasing factor may play an important role in modulating synaptic plasticity in the hippocampus.
To examine whether corticotropin-releasing factor-induced potentiation involves protein synthesis, we have administered RNA and protein synthesis inhibitors, actinomycin D and emetine respectively, to the dentate gyrus before corticotropin-releasing factor administration . Results indicated that actinomycin D and emetine did not affect synaptic transmission of hippocampal neurons by themselves, while both of them markedly decreased corticotropin-releasing factor-induced potentiation. These results suggest tha
t new protein synthesis is indeed involved in the mechanism of corticotropin-releasing factor-induced potentiation.
| Identifer | oai:union.ndltd.org:TW/086NDMC0105017 |
| Date | January 1998 |
| Creators | Wang Hai-Long, 王海龍 |
| Contributors | Emeny H. Y. Lee, 李小媛 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 0 |
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