Somers D L, Beckstead R M
Department of Anatomy and Cell Biology, Medical University of South Carolina, Charleston 29425.
Brain Res Mol Brain Res. 1990 Jul;8(2):143-58. doi: 10.1016/0169-328x(90)90059-m.
Because excitatory amino acid (EAA) neurotransmission has been implicated in long-term postsynaptic events, we conducted an initial study to determine whether or not the EAA-utilizing corticostriatal projection might influence peptide biosynthesis in neurons of the rat's basal ganglia. The content of EAAs in the caudatoputamen was reduced by frontal cortical ablation or by chronic intracerebroventricular infusion of methionine sulfoximine (MS). At 7 days following cortical ablation striatal Asp and Glu were reduced by 15% and 24%, respectively, while MS infusion (24 micrograms/day) for 7 days reduced synaptosomal levels of Asp by 61% and Glu by 48%. With either treatment, quantitative radioimmunocytochemistry revealed that substance P (SP) in the substantia nigra was increased by approximately 38%, while Met5-enkephalin (ME) in the globus pallidus was not changed. In situ hybridization with oligonucleotide probes revealed changes in the rostral striatum of preprotachykinin (PPT) and preproenkephalin (PPE) mRNA levels: cortical ablation reduced PPT mRNA by 17% and PPE mRNA by 20% dorsally, while it increased PPE mRNA (but not PPT mRNA) by 23% ventrally. Likewise, the infusion of MS decreased PPT (32%) and PPE mRNA (28%) dorsally, and increased PPE mRNA (50%) ventrally. In addition to the 7 day time point, the same measurements of EAAs, peptides and mRNAs were made at 14, 21 and 28 days after cortical excisions. At 14 days, the level of striatal Asp had returned to control value, but Glu remained depressed by 21%; nigral SP remained increased by 24%, and pallidal ME decreased by 15%. PPT and PPE mRNA remained depressed dorsally by 15% and 25%, respectively, while the increase in PPE mRNA noted ventrally at 7 days had returned to control values by 14 days. With the exception of Glu, which remained depressed by 18% at 21 and 28 days, all other values had returned to control levels by 21 days. The results indicate that a large reduction in EAA neurotransmission can influence differentially the steady-state levels of neuropeptides in striatal neurons and this change is brought about, at least in part, by an alteration in gene transcription.
由于兴奋性氨基酸（EAA）神经传递与长期突触后事件有关，我们进行了一项初步研究，以确定利用EAA的皮质纹状体投射是否可能影响大鼠基底神经节神经元中的肽生物合成。通过额叶皮质切除或通过慢性脑室内注入蛋氨酸亚砜亚胺（MS）降低尾状壳核中EAA的含量。在皮质切除后7天，纹状体中的天冬氨酸（Asp）和谷氨酸（Glu）分别降低了15%和24%，而连续7天注入MS（24微克/天）使突触体中天冬氨酸水平降低了61%，谷氨酸水平降低了48%。无论采用哪种治疗方法，定量放射免疫细胞化学显示黑质中的P物质（SP）增加了约38%，而苍白球中的甲硫氨酸脑啡肽（ME）没有变化。用寡核苷酸探针进行原位杂交显示，前速激肽原（PPT）和前脑啡肽原（PPE）mRNA水平在纹状体前部发生了变化：皮质切除使背侧PPT mRNA降低了17%，PPE mRNA降低了20%，而腹侧PPE mRNA增加了23%（但PPT mRNA未增加）。同样，注入MS使背侧PPT（32%）和PPE mRNA（28%）降低，腹侧PPE mRNA增加（50%）。除了7天这个时间点外，在皮质切除后14、21和28天对EAA、肽和mRNA进行了相同的测量。在14天时，纹状体中天冬氨酸水平已恢复到对照值，但谷氨酸仍降低21%；黑质中SP仍增加24%，苍白球中ME降低15%。PPT和PPE mRNA在背侧分别仍降低15%和25%，而在7天时腹侧观察到的PPE mRNA增加在14天时已恢复到对照值。除了谷氨酸在21天和28天时仍降低18%外，所有其他值在21天时已恢复到对照水平。结果表明，EAA神经传递的大幅减少可对纹状体神经元中神经肽的稳态水平产生不同影响，并且这种变化至少部分是由基因转录改变引起的。
