Ward N L, Stanford L E, Brown R E, Hagg T
Department of Anatomy and Neurobiology, Tupper Building, Dalhousie University, Halifax, N.S, Canada.
Neurobiol Aging. 2000 Jan-Feb;21(1):125-34. doi: 10.1016/s0197-4580(00)00087-7.
Cholinergic medial septum neurons express TrkA and p75 nerve growth factor receptor (p75(NGFR)) and interactions between TrkA and p75(NGFR) are necessary for high-affinity binding and signaling of nerve growth factor (NGF) through TrkA. In adult p75(NGFR)-deficient (-/-) mice, retrograde transport of NGF and other neurotrophins by these neurons is greatly reduced, however, these neurons maintain their cholinergic phenotype and size. Reduced transport of NGF has been proposed to play a role in Alzheimer's disease. Here, we investigated whether chronic and long-term absence of p75(NGFR) (and possibly reduced NGF transport and TrkA binding) would affect the cholinergic septohippocampal system during aging in mice. In young (6-8 months), middle aged (12-18 months), and aged (19-23 months) 129/Sv control mice the total number of choline acetyltransferase-positive medial septum neurons and the mean diameter and cross sectional area of the cholinergic cell bodies were similar. The cholinergic hippocampal innervation, as measured by the density of acetylcholinesterase-positive fibers in the outer molecular layer of the dentate gyrus was also similar across all ages. These parameters also did not change during aging in p75(NGFR) -/- mice and the number and size of the choline acetyltransferase-positive neurons and the cholinergic innervation density were largely similar as in control mice at all ages. These results suggest that p75(NGFR) does not play a major role in the maintenance of the number or morphology of the cholinergic basal forebrain neurons during aging of these mice. Alternatively, p75(NGFR) -/- mice may have developed compensatory mechanisms in response to the absence of p75(NGFR).
胆碱能内侧隔核神经元表达酪氨酸激酶A（TrkA）和p75神经生长因子受体（p75(NGFR)），TrkA与p75(NGFR)之间的相互作用对于神经生长因子（NGF）通过TrkA进行高亲和力结合和信号传导是必需的。在成年p75(NGFR)基因敲除（-/-）小鼠中，这些神经元对NGF和其他神经营养因子的逆行运输大大减少，然而，这些神经元维持其胆碱能表型和大小。有人提出NGF运输减少在阿尔茨海默病中起作用。在这里，我们研究了长期缺乏p75(NGFR)（以及可能减少的NGF运输和TrkA结合）是否会在小鼠衰老过程中影响胆碱能隔-海马系统。在年轻（6-8个月）、中年（12-18个月）和老年（19-23个月）的129/Sv对照小鼠中，胆碱乙酰转移酶阳性内侧隔核神经元的总数以及胆碱能细胞体的平均直径和横截面积相似。通过齿状回外分子层中乙酰胆碱酯酶阳性纤维密度测量的胆碱能海马神经支配在所有年龄段也相似。在p75(NGFR) -/-小鼠衰老过程中，这些参数也没有变化，并且胆碱乙酰转移酶阳性神经元的数量和大小以及胆碱能神经支配密度在所有年龄段与对照小鼠基本相似。这些结果表明，在这些小鼠衰老过程中，p75(NGFR)在维持胆碱能基底前脑神经元的数量或形态方面不起主要作用。或者，p75(NGFR) -/-小鼠可能已经针对p75(NGFR)的缺失发展出了补偿机制。
