Lauder J M, Schambra U B
Department of Cell Biology and Anatomy, University of North Carolina School of Medicine, Chapel Hill 27599-7090, USA.
Environ Health Perspect. 1999 Feb;107 Suppl 1(Suppl 1):65-9. doi: 10.1289/ehp.99107s165.
In the adult nervous system, neurotransmitters mediate cellular communication within neuronal circuits. In developing tissues and primitive organisms, neurotransmitters subserve growth regulatory and morphogenetic functions. Accumulated evidence suggests that acetylcholine, (ACh), released from growing axons, regulates growth, differentiation, and plasticity of developing central nervous system neurons. In addition to intrinsic cholinergic neurons, the cerebral cortex and hippocampus receive extensive innervation from cholinergic neurons in the basal forebrain, beginning prenatally and continuing throughout the period of active growth and synaptogenesis. Acute exposure to ethanol in early gestation (which prevents formation of basal forebrain cholinergic neurons) or neonatal lesioning of basal forebrain cholinergic neurons, significantly compromises cortical development and produces persistent impairment of cognitive functions. Neonatal visual deprivation alters developmental expression of muscarinic acetylcholine receptors (mAChR) in visual cortex, whereas local infusion of mAChR antagonists impairs plasticity of visual cortical neurons. These findings raise the possibility that exposure to environmental neurotoxins that affect cholinergic systems may seriously compromise brain development and have long-lasting morphologic, neurochemical, and functional consequences.
在成体神经系统中，神经递质介导神经元回路内的细胞通讯。在发育中的组织和原始生物体中，神经递质发挥生长调节和形态发生功能。越来越多的证据表明，生长轴突释放的乙酰胆碱（ACh）可调节发育中的中枢神经系统神经元的生长、分化和可塑性。除了内在的胆碱能神经元外，大脑皮层和海马体从基底前脑的胆碱能神经元接受广泛的神经支配，这种支配在产前就已开始，并在活跃生长和突触形成期间持续存在。孕期早期急性接触乙醇（这会阻止基底前脑胆碱能神经元的形成）或新生动物基底前脑胆碱能神经元受损，会显著损害皮层发育并导致认知功能的持续损伤。新生动物视觉剥夺会改变视觉皮层中毒蕈碱型乙酰胆碱受体（mAChR）的发育表达，而局部注入mAChR拮抗剂会损害视觉皮层神经元的可塑性。这些发现增加了一种可能性，即接触影响胆碱能系统的环境神经毒素可能会严重损害大脑发育，并产生长期的形态学、神经化学和功能后果。
