Systems Biology Program, Centre for Genomic Regulation (CRG), Barcelona E-08003, Spain; University Pompeu Fabra (UPF), Spain; CIBER de Enfermedades Raras (CIBERER), Barcelona E-08003, Spain.
Systems Biology Program, Centre for Genomic Regulation (CRG), Barcelona E-08003, Spain; University Pompeu Fabra (UPF), Spain; CIBER de Enfermedades Raras (CIBERER), Barcelona E-08003, Spain.
Neurosci Biobehav Rev. 2014 Oct;46 Pt 2:315-25. doi: 10.1016/j.neubiorev.2014.05.012. Epub 2014 May 29.
The involvement of the cholinergic system in learning, memory and attention has long been recognized, although its neurobiological mechanisms are not fully understood. Recent evidence identifies the endogenous cholinergic signaling via nicotinic acetylcholine receptors (nAChRs) as key players in determining the morphological and functional maturation of the glutamatergic system. Here, we review the available experimental and clinical evidence of nAChRs contribution to the establishment of the glutamatergic system, and therefore to cognitive function. We provide some clues of the putative underlying molecular mechanisms and discuss recent human studies that associate genetic variability of the genes encoding nAChR subunits with cognitive disorders. Finally, we discuss the new avenues to therapeutically targeting nAChRs in persons with cognitive dysfunction for which the α7-nAChR subunit is an important etiological mechanism.
胆碱能系统在学习、记忆和注意中的作用早已被认识，但其神经生物学机制尚不完全清楚。最近的证据表明，通过烟碱型乙酰胆碱受体（nAChRs）的内源性胆碱能信号是决定谷氨酸能系统形态和功能成熟的关键因素。在这里，我们回顾了 nAChRs 对谷氨酸能系统建立的作用的现有实验和临床证据，因此也回顾了对认知功能的作用。我们提供了一些潜在的分子机制的线索，并讨论了最近将编码 nAChR 亚基的基因的遗传变异性与认知障碍相关联的人类研究。最后，我们讨论了治疗具有认知功能障碍的个体的新途径，其中α7-nAChR 亚基是一个重要的病因机制。
