生物物理與神經生物學前沿學術報告
報告題目:Altered release of neurotransmitters and brain-derived neurotrophic factor (BDNF) in terminals in cortical neurons of Huntington’s disease
報告人:Hyokeun Park, Ph.D
Professor of Division of Life Science and Department of Physics
The Hong Kong University of Science and Technology
時間：2018年12月18日（周二），上午：10:30-11:30
地點：西區生物樓429會議室
主辦單位：中國科學院腦功能與腦疾病重點實驗室
中國科學技術大學生命科學學院
合肥微尺度物質科學國家研究中心集成影像中心
報告簡介：Huntington’s disease (HD) is a genetic neurodegenerative disorder caused by an abnormal expansion of CAG trinucleotide repeats in the huntingtin gene. Mutant huntingtin (mhtt) proteins induce the progressive neuronal loss from the striatum and cortex, despite of their ubiquitous expression. One possible mechanism of this selective degeneration is that dysfunction in synaptic transmission in the corticostriatal synapses could lead to the selective degeneration of these striatal neurons. However, the release of neurotransmitters and BDNF as an input of corticostriatal synapses in HD has not fully understood yet. Thus, we examined the release of neurotransmitters and BDNF during the stimulation at single presynaptic terminals in primary cortical neurons using real-time imaging with FM 1-43 labeled synaptic vesicles and BDNF-pHluorin. The released neurotransmitters at presynaptic terminals in heterozygous neurons of a HD knock-in mouse model (Q175) were significantly higher than wild-type neurons. BDNF release was markedly decreased in the cortical neurons of zQ175 mice and total internal-reflection fluorescence microscopy revealed several release patterns of single BDNF-containing vesicles, with distinct kinetics and prevalence, in cultured cortical HD neurons. Notably, a smaller proportion of single BDNF-containing vesicles underwent full release in HD neurons than in wild-type neurons. This decreased release of BDNF in cortical neurons might lead to decreased BDNF levels in the striatum because the striatum receives BDNF mainly from the cortex. Our findings suggest a potential mechanism for the vulnerability of striatal neurons in HD, considering the crucial roles of neurotransmitter and BDNF in promoting synaptic activity and neuron survival, and offer new insights into the pathogenic mechanisms underlying neuron degeneration in HD.