贾 宁,刘子赫,贾瑞华,李 瑞,张正平,王 璐,高 方.兴奋性突触传入对皮层神经元形态发育的影响[J].,2019,19(17):3257-3262 |
兴奋性突触传入对皮层神经元形态发育的影响 |
Effect of Excitatory Synaptic Afferent Signal on the Morphological Development of Cortical Neurons |
投稿时间:2019-03-23 修订日期:2019-04-18 |
DOI:10.13241/j.cnki.pmb.2019.17.011 |
中文关键词: 抑制性神经元 兴奋性神经元 AMPA受体 NMDA受体 形态发育 |
英文关键词: Inhibitory interneuron Excitatory neuron AMPA receptor NMDA receptor Morphological development |
基金项目:陕西省自然科学基金项目(2018KW-063);延安大学资政育人项目(YDZZYB17-092) |
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中文摘要: |
摘要 目的:探讨离子型谷氨酸受体中的AMPA受体(?琢-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor, AMPA受体)和NMDA受体(N-methyl-D-aspartic acid receptor)对抑制性中间神经元以及兴奋性神经元的形态发育的影响。方法:采用原代培养皮层神经元,通过药物干预AMPA受体和/或NMDA受体的方法阻断神经元的离子型谷氨酸受体,并采用GAD67-GFP鼠的绿色荧光来显示混合细胞群中抑制性神经元、CaMKII免疫荧光染色显示兴奋性神经元。结果:当阻断AMPA和/或NMDA受体时,光镜下显示神经元网络的密度降低,且随着药物浓度的增加,神经元网络的变化更明显。对于GFP阳性的抑制性神经元,当阻断AMPA受体时,神经元突起分支数降低至对照组的约65%(低浓度)和55%(高浓度),突起长度缩短至对照组的大约43%(低浓度)和36%(高浓度);当阻断NMDA受体时,分支数降低至约70%(低浓度)和45%(高浓度),长度缩短至约43%(低浓度)和31%(高浓度);联合用药时,分支数和长度分别为对照的约42%和38%。对于CaMKII阳性的兴奋性神经元,尽管变化程度稍弱,但其形态也出现类似变化。当阻断AMPA受体时,神经元的分支数降低至对照组的64%(高浓度),突起长度变化不大;当阻断NMDA受体时,分支数降低至约50%(高浓度),长度缩短至约77%(低浓度)和71%(高浓度);联合用药时,分支数和长度分别为对照的约69%和62%。结论:在神经元发育的过程中,离子型谷氨酸受体介导的兴奋性突触传入可影响抑制性神经元和兴奋性神经元的形态发育,最终对神经环路的形成发挥重要的调控作用。 |
英文摘要: |
ABSTRACT Objective: To detect the effects of AMPA receptor (?琢-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor) and NMDA receptor (N-methyl-D-aspartic acid receptor), two of ionotropic glutamate receptors, on the morphological development of inhibitory interneurons and excitatory neurons. Methods: Primary cultured cortical neurons were treated with drugs to interfere with AMPA receptors and/or NMDA receptors, to block neuronal ionotropic glutamate receptors. Neurons of each group were observed, and the inhibitory neurons were displayed by green fluorescence in GAD67-GFP transgenic mice while the excitatory neurons were showed by CaMKII immunofluorescence staining. Results: When AMPA and/or NMDA receptors were blocked, the density of the neural network decreased when observed under light microscope, and the degree of decreasing became even more obvious with the increase of drug concentration. For GFP-positive inhibitory interneurons, when AMPA receptors were blocked, the number of neuronal branches decreased to 65% (low concentration) and 55% (high concentration) of the control group, and the length of processes was shortened to 43% (low concentration) and 36% (high concentration) of the control. When NMDA receptors were blocked, the number of branches decreased to 70% (low concentration) and 45% (high concentration), and the length decreased to 43% (low concentration) and 31% (high concentration). And when AMPA and NMDA receptors were blocked together, the number of branches decreased to 42% and the length decreased to 38%. For CaMKII-positive excitatory neurons, although the degree was weaker, the neurons showed similar changes in morphology, with reduced number of branches and shortened length of processes. When AMPA receptors were blocked, the number of branches decreased to 64% (high concentration), and the length didn't vary too much. When NMDA receptors were blocked, the number of branches decreased to 50% (high concentration), and the length decreased to 77% (low concentration) and 71% (high concentration). And when AMPA and NMDA receptors were blocked together, the number of branches decreased to 69% and the length decreased to 62%. Conclusion: During neuronal development, the excitatory synaptic afferent signal mediated by ionic glutamate receptors showed effects on the morphological development of inhibitory interneurons and excitatory neurons, and finally plays an important regulatory role in the formation of neural circuits. |
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