| Summary: | 碩士 === 國立成功大學 === 藥理學研究所 === 92 === Brain-derived neurotropic factor (BDNF) and its receptor tyrosine kinase (TrkB) play important roles in neural plasticity, long-term potentiation and memory formation. One of the best-characterized neurotrophin-activated signal transduction pathways is the extracellular -regulated kinase / mitogen-activated protein kinase (ERK / MAPK) cascade. We have previously reported that fear conditioning led to the phosphorylation of ERK. The purpose of this study is to investigate whether BDNF and its downstream pathways are involved in the consolidation of fear memory measured with fear-potentiated startle paradigm.
Neuronal tissues taken from the lateral and basolateral amygdala of the conditioned rats showed an increase in the BDNF protein expression as compared with the control. Fear training also led to an increase in the phosphorylation of TrkB receptor, ERK, Akt, PLCγ1 and the activation of Ras. In behavioral tests, rats given intra-amygdala infusion of Trk, MEK, PI3K and Ras inhibitor had impaired memory.Direct application of BDNF to the amygdala enhanced the startle potentiation and the enhancememt is abolished by pre-treatment of Trk, MEK, PI3K and Ras inhibitor.
Treatment of amygdala slices with BDNF increased the levels of p- ERK, Akt and PLCγ1. Pretreatment of amygdala slices with Ras and PI3K inhibitor blocked the activation of ERK induced by BDNF.PI3K activation induced by BDNF was blocked by Ras inhibitor.
On the other hand, fear conditioning caused a Trk-dependent increase of cell surface expression of GluR1 in the amygdala.
Taken together, these results demonstrate a functional role of BDNF in fear learning and provide candidate signaling pathways coupled to TrkB receptor activation.
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