Co-localization of high-affinity neurotrophin receptors in nucleus basalis of Meynert neurons and their differential reduction in Alzheimer's disease

被引:119
作者
Salehi, A
Verhaagen, J
Dijkhuizen, PA
Swaab, DF
机构
[1] NETHERLANDS INST BRAIN RES,GRAD SCH NEUROSCI AMSTERDAM,NL-1105 AZ AMSTERDAM,NETHERLANDS
[2] SHAHID BEHESHTI UNIV MED SCI,FAC MED,DEPT PHYSIOL,TEHRAN,IRAN
[3] RUDOLF MAGNUS INST NEUROSCI,NL-3508 TA UTRECHT,NETHERLANDS
关键词
trk receptors; Alzheimer; neurotrophin; nucleus basalis; NGF;
D O I
10.1016/0306-4522(96)00273-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
It has been suggested that degeneration of neurons in Alzheimer's disease is the result of diminished trophic support. However, so far no evidence has been forwarded that neuronal degeneration in Alzheimer's disease is causally related to insufficient production of neurotrophins. The present study deals with (i) the expression and co-localization of tyrosine kinase receptors (trks) in the human nucleus basalis of Meynert and (ii) alterations of these receptors in Alzheimer's disease in the nucleus basalis of Meynert, an area severely affected in Alzheimer's disease. The expression of trkA, trkB and trkC in the nucleus basalis of Meynert of control and Alzheimer's disease brains was studied using three polyclonal antibodies specifically recognizing the extracellular domain of trkA, trkB and trkC. Brain material of eight controls and seven Alzheimer's disease patients was obtained at autopsy, embedded in paraffin and stained immunocytochemically. Using an image analysis system, we determined the proportion of trk neurons expressing the different trk receptors in controls and Alzheimer's disease patients. In control brains, trkA, trkB and trkC were differentially expressed in numerous nucleus basalis of Meynert neurons. The highest proportion of neurons was found to express trkB (75%), followed by trkC (58%) and trkA (54%). Furthermore, using consecutive sections, a clear co-localization of trk receptors was observed in the same neurons. The highest degree of co-localization was observed between trkA and trkB. In Alzheimer's disease patients, the number of immunoreactive neurons and the staining intensity of individual neurons was reduced dramatically. Reduction in the proportion of neurons expressing trkA was 69%, in trkB 47% and in trkC 49%, which indicated a differential reduction in the amount of trk receptors in Alzheimer's disease. These observations indicate that nucleus basalis of Meynert neurons can be supported by more than one neurotrophin and that the degeneration of these neurons in Alzheimer's disease is associated with a decreased expression of trk receptors, suggesting a decreased neurotrophin responsiveness of nucleus basalis of Meynert neurons in Alzheimer's disease. Copyright (C) 1996 IBRO.
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收藏
页码:373 / 387
页数:15
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