Sobreviela T, Jaffar S, Mufson E J
Department of Neurological Sciences, Center for Brain Repair, Rush Presbyterian-St Luke's Medical Center, Chicago, IL 60612, USA.
Neuroscience. 1998 Nov;87(2):447-61. doi: 10.1016/s0306-4522(98)00153-5.
Cholinergic basal forebrain neurons appear to play a key role in cognition and attention. In rat, basal forebrain neurons express multiple proteins including the high-affinity signal transducing tyrosine kinase A receptor for nerve growth factor, the neuropeptide galanin and nitric oxide synthase, a marker for the novel neurotransmitter nitric oxide. The present study was undertaken to define the relationship between neurons expressing each of these markers within the medial septum-vertical limb of the diagonal band, horizontal limb of the diagonal band and nucleus basalis in colchicine pre-treated rats. Tyrosine kinase A-immunopositive neurons were seen throughout all subfields of the basal forebrain. In contrast, nitric oxide synthase- and galanin-immunoreactive neurons were mainly distributed within the septal-diagonal band complex. Co-localization experiments revealed that virtually all nitric oxide synthase-positive neurons (visualized by nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry) also contained tyrosine kinase A, whereas many fewer tyrosine kinase A neurons were nicotinamide adenine dinucleotide phosphate-diaphorase positive within the medial septum-vertical limb of the diagonal band. Within the horizontal limb of the diagonal band, numerous nicotinamide adenine dinucleotide phosphate-diaphorase neurons expressed tyrosine kinase A, whereas only a small number of tyrosine kinase A neurons contained nicotinamide adenine dinucleotide phosphate-diaphorase. Within the nucleus basalis very few neurons were nicotinamide adenine dinucleotide phosphate-diaphorase reactive, and a minor number contained tyrosine kinase A. Additional co-localization experiments revealed minor percentages of neurons containing nicotinamide adenine dinucleotide phosphate-diaphorase and galanin immunoreactivity within the various subfields of the basal forebrain. Within the horizontal limb of the diagonal band minor numbers of nicotinamide adenine dinucleotide phosphate-diaphorase-reactive perikarya displayed galanin. Similarly, only a few galanin-containing neurons expressed nicotinamide adenine dinucleotide phosphate-diaphorase. The existence of tyrosine kinase A, nitric oxide synthase and galanin within select neuronal subgroups of the cholinergic basal forebrain suggests that these perikarya are responsive to a complex set of chemical signals. A greater understanding of the chemical signature of the cholinergic basal forebrain neurons will provide the insight required to develop novel pharmacological approaches aimed at preventing or slowing the degenerative processes that effect these neurons in aging and pathologic disorders.
胆碱能基底前脑神经元似乎在认知和注意力方面发挥着关键作用。在大鼠中，基底前脑神经元表达多种蛋白质，包括神经生长因子的高亲和力信号转导酪氨酸激酶A受体、神经肽甘丙肽和一氧化氮合酶，一氧化氮合酶是新型神经递质一氧化氮的标志物。本研究旨在确定秋水仙碱预处理大鼠内侧隔-斜角带垂直支、斜角带水平支和基底核中表达这些标志物的神经元之间的关系。酪氨酸激酶A免疫阳性神经元可见于基底前脑的所有亚区。相比之下，一氧化氮合酶和甘丙肽免疫反应性神经元主要分布在隔-斜角带复合体中。共定位实验显示，几乎所有一氧化氮合酶阳性神经元（通过烟酰胺腺嘌呤二核苷酸磷酸-黄递酶组织化学显示）也含有酪氨酸激酶A，而在斜角带内侧隔-垂直支中，酪氨酸激酶A神经元中烟酰胺腺嘌呤二核苷酸磷酸-黄递酶阳性的较少。在斜角带水平支内，大量烟酰胺腺嘌呤二核苷酸磷酸-黄递酶神经元表达酪氨酸激酶A，而只有少数酪氨酸激酶A神经元含有烟酰胺腺嘌呤二核苷酸磷酸-黄递酶。在基底核内，很少有神经元对烟酰胺腺嘌呤二核苷酸磷酸-黄递酶有反应，少数含有酪氨酸激酶A。额外的共定位实验显示，在基底前脑的各个亚区内，含有烟酰胺腺嘌呤二核苷酸磷酸-黄递酶和甘丙肽免疫反应性的神经元占比很小。在斜角带水平支内，少数烟酰胺腺嘌呤二核苷酸磷酸-黄递酶反应性的胞体显示有甘丙肽。同样，只有少数含甘丙肽的神经元表达烟酰胺腺嘌呤二核苷酸磷酸-黄递酶。胆碱能基底前脑特定神经元亚群中存在酪氨酸激酶A、一氧化氮合酶和甘丙肽，这表明这些胞体对一组复杂的化学信号有反应。对胆碱能基底前脑神经元化学特征的更深入了解将为开发旨在预防或减缓衰老和病理疾病中影响这些神经元的退行性过程的新型药理学方法提供所需的见解。
