ADENOSINE RECEPTORS IN DEVELOPING RAT BRAIN

腺苷通过特定的膜结合受体来调节 中枢神经系统的活动。人们对此知之甚少 腺苷受体的发育外观，或 大脑发育过程中腺苷受体的操作。这个 该方案中的实验将检验两个假设：(1)泛函 腺苷受体系统存在于胎鼠脑内，以及(2) 腺苷受体在发育过程中的操纵改变基因 在胎儿纹状体中的表达。敏感度的发展 通过研究腺苷在大脑中的表达，将证明大脑中的腺苷 Northern印迹和原位杂交检测腺苷受体mRNAs， 用配基放射自显影技术结合腺苷受体和腺苷 受体在体外对腺酰环化酶活性的影响。 随后的研究将考察 脑啡肽原表达细胞和A2a-腺苷受体表达细胞 发育中的纹状体。最后，用腺苷受体操纵 这种拮抗剂咖啡因将被用来检查腺苷是否 受体调节胎儿纹状体的基因表达。总而言之， 这项提案中的实验将证明 从胎儿脑到腺苷，并提供了对 腺苷受体调控对纹状体发育的影响。 在成人大脑中，腺苷调节神经递质的释放和 电活动。这些事件可能对建立 并在发育中的大脑中维持突触连接。因此， 腺苷和腺苷受体可能在正常 神经系统的发育。腺苷在产前的变化 受体功能可能会微妙地改变这些重要的神经元相互作用， 导致学习障碍和其他障碍的发生 神经系统的功能。

Adenosine acts via specific, membrane-bound receptors to modulate the activity of the central nervous system. Little is known about the developmental appearance of adenosine receptors, or the effects of adenosine receptor manipulation during brain development. The experiments in this proposal will test two hypotheses: (1) a functional adenosine receptor systems are present in fetal rat brain, and (2) manipulation of adenosine receptors during development alters gene expression in the fetal striatum. The development of sensitivity to adenosine in the brain will be documented by studying expression of adenosine receptor mRNAs by Northern blot and in situ hybridization, adenosine receptor binding using ligand autoradiography, and adenosine receptor-mediated effects on adenylyl cyclase activity in vitro. Subsequent studies will examine the anatomical relationship between proenkephalin-expressing and A2a-adenosine receptor-expressing cells in the developing striatum. Finally, adenosine receptor manipulation with the antagonist, caffeine, will be performed to examine whether adenosine receptor regulate gene expression in the fetal striatum. Collectively, the experiments in this proposal will document the sensitivity of the fetal brain to adenosine, and provide an initial examination of the effects of adenosine receptor manipulation on striatal development. In the adult brain, adenosine modulates neurotransmitter release and electrical activity. These events are likely important in establishing and maintaining synaptic connections in the developing brain. Thus, adenosine and adenosine receptors may play important roles in the normal development of the nervous system. Prenatal alterations in adenosine receptor function may subtly alter these important neuronal interactions, contributing to the genesis of learning disabilities and other disorders of nervous system function.