Volume Transmission in Central Dopamine and Noradrenaline Neurons and Its Astroglial Targets
Volume Transmission in Central Dopamine and Noradrenaline Neurons and Its Astroglial Targets
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DOI：
10.1007/s11064-015-1574-5
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发表时间：
2015-12-01
影响因子：
4.4
通讯作者：
Borroto-Escuela, Dasiel O.
中科院分区：
文献类型：
--
作者：
Fuxe, Kjell;Agnati, Luigi F.;Borroto-Escuela, Dasiel O.
早在20世纪60年代，脑干多巴胺（DA）和去甲肾上腺素（NA）神经元的结构和药理学与中枢神经系统（CNS）的大量DA和NA终丛的形成表明，它们可能不仅通过突触传递进行通信。在20世纪80年代，体积传递（VT）理论被引入作为CNS中与突触传递一起的主要通信。VT是细胞外和脑脊液中化学信号的传递，如递质、调节剂等，沿沿着能量梯度移动，使VT信号的扩散和流动成为可能。VT主要通过突触和突触外异源受体复合物中的直接受体-受体相互作用及其信号级联与突触传递相互作用。DA和NA神经元在体树突和终末水平上专门用于突触外VT。释放的儿茶酚胺靶向神经细胞、星形胶质细胞和小胶质细胞上的多种DA和肾上腺素能亚型，这些细胞是建立中枢神经系统神经胶质网络的营养单位的主要细胞成分。DA和NA VT不仅可以调节突触传递的强度，还可以调节与神经元-胶质细胞相互作用高度相关的星形胶质细胞和小胶质细胞的VT信号。以星形胶质细胞为靶点的儿茶酚胺VT可以调节在神经能量学、淋巴系统、中枢肾素-血管紧张素系统和长距离钙波产生中观察到的星形胶质细胞的基本功能。此外，星形胶质细胞和小胶质细胞DA和肾上腺素能受体亚型介导的DA和NAVT可以是重要的药物靶点在神经和精神疾病。
Already in the 1960s the architecture and pharmacology of the brainstem dopamine (DA) and noradrenaline (NA) neurons with formation of vast numbers of DA and NA terminal plexa of the central nervous system (CNS) indicated that they may not only communicate via synaptic transmission. In the 1980s the theory of volume transmission (VT) was introduced as a major communication together with synaptic transmission in the CNS. VT is an extracellular and cerebrospinal fluid transmission of chemical signals like transmitters, modulators etc. moving along energy gradients making diffusion and flow of VT signals possible. VT interacts with synaptic transmission mainly through direct receptor-receptor interactions in synaptic and extrasynaptic heteroreceptor complexes and their signaling cascades. The DA and NA neurons are specialized for extrasynaptic VT at the soma-dendrtitic and terminal level. The catecholamines released target multiple DA and adrenergic subtypes on nerve cells, astroglia and microglia which are the major cell components of the trophic units building up the neural-glial networks of the CNS. DA and NA VT can modulate not only the strength of synaptic transmission but also the VT signaling of the astroglia and microglia of high relevance for neuron-glia interactions. The catecholamine VT targeting astroglia can modulate the fundamental functions of astroglia observed in neuroenergetics, in the Glymphatic system, in the central renin-angiotensin system and in the production of long-distance calcium waves. Also the astrocytic and microglial DA and adrenergic receptor subtypes mediating DA and NA VT can be significant drug targets in neurological and psychiatric disease.