Jung A B, Bennett J P
Department of Neurology, University of Virginia School of Medicine, Charlottesville 22908, USA.
Brain Res Dev Brain Res. 1996 Jul 20;94(2):133-43. doi: 10.1016/0165-3806(96)00035-1.
Known neurotrophins in the nigrostriatal system include brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) which exert biological effects after high affinity binding to their respective tyrosine kinase receptors, trkB and trkC. We measured striatal trkBTK+ and trkC mRNAs in rat brain sections with in situ hybridization histochemistry. Both trkBTK+ and trkC transcripts were present in the striatal anlage at embryonic day (E) 14 or 16. Striatal trkBTK+ mRNA levels increased to a peak in the late prenatal period and gradually declined in the postnatal period. In contrast, striatal trkC mRNA levels peaked on E16, then declined to fairly constant levels. Striatal trkBTK+ gene expression increased from the medial to lateral quadrants throughout development, whereas trkC mRNA increased from the lateral to medial quadrants prenatally but increased from the dorsal to ventral quadrants on postnatal days (P) 1 and 3. The distinct spatiotemporal developmental profiles of trkBTK+ and trkC mRNA suggest that their respective ligands BDNF and NT-4/5, and NT-3, may have specialized functions in striatal neuronal development. Because neurotransmitters may regulate neurotrophin function in developing neural systems, we treated rats of various ages with the indirect dopamine agonist cocaine and measured the effects of cocaine treatment on transcription of the trk genes. Acute 1 h cocaine treatment increased trkBTK+ and trkC mRNA levels in the P5 striatum but not in the E15, E20, or adult striatum. The trkBTK+ effect was blocked by pretreatment with the D1 receptor antagonist, SCH23390, and was not affected by pretreatment with the D2 receptor antagonist, eticlopride. In contrast, trkC regulation may be mediated by independent stimulation of D1 and D2 receptors. We hypothesize that the endogenous nigrostriatal neurotransmitter dopamine can modulate striatal neurotrophin responsiveness and thereby influence striatal neuronal development during a defined developmental period.
黑质纹状体系统中已知的神经营养因子包括脑源性神经营养因子（BDNF）和神经营养因子-3（NT-3），它们在与各自的酪氨酸激酶受体trkB和trkC高亲和力结合后发挥生物学作用。我们用原位杂交组织化学方法检测大鼠脑切片中的纹状体trkBTK+和trkC mRNA。在胚胎第14天或16天，纹状体原基中同时存在trkBTK+和trkC转录本。纹状体trkBTK+ mRNA水平在产前后期升至峰值，产后逐渐下降。相比之下，纹状体trkC mRNA水平在胚胎第16天达到峰值，然后降至相当稳定的水平。在整个发育过程中，纹状体trkBTK+基因表达从内侧象限向外侧象限增加，而trkC mRNA在产前从外侧象限向内侧象限增加，但在出生后第1天和第3天从背侧象限向腹侧象限增加。trkBTK+和trkC mRNA独特的时空发育模式表明，它们各自的配体BDNF和NT-4/5以及NT-3可能在纹状体神经元发育中具有特定功能。由于神经递质可能调节发育中的神经系统中的神经营养因子功能，我们用间接多巴胺激动剂可卡因处理不同年龄的大鼠，并测量可卡因处理对trk基因转录的影响。急性1小时可卡因处理增加了出生后第5天纹状体中的trkBTK+和trkC mRNA水平，但在胚胎第15天、第20天或成年纹状体中未增加。trkBTK+效应被D1受体拮抗剂SCH23390预处理阻断，且不受D2受体拮抗剂依替必利预处理的影响。相比之下，trkC的调节可能由D1和D2受体的独立刺激介导。我们假设内源性黑质纹状体神经递质多巴胺可以调节纹状体神经营养因子反应性，从而在特定发育时期影响纹状体神经元发育。
