Dubus P, Faucheux B, Boissière F, Groppi A, Vital C, Vital A, Agid Y, Hirsch E C, Merlio J P
Laboratoire d'Histologie-Embryologie, EA 2406 Université de Bordeaux 2, Bordeaux Cedex, 33076, France.
Exp Neurol. 2000 Oct;165(2):285-94. doi: 10.1006/exnr.2000.7447.
The TrkAII tyrosine kinase receptor differs from the TrkAI isoform by an insertion of six amino acids in the extracellular domain. We used RT-PCR to determine their respective distribution in rat and human brain. Only trkAII transcripts were detected in 12 rat brain regions, while both trkAI and trkAII transcripts were detected in the cerebellum and pituitary gland. In human, both trkAI and trkAII transcripts were detected in the frontal, temporal, and occipital cortex and thalamus, while only trkAI transcripts were detected in the hippocampus and cerebellum. In the caudate and putamen, trkAII transcripts were exclusively detected. Thereafter, we studied the expression of TrkA isoforms in the striatum of five patients with Alzheimer's disease (AD), four patients with non-AD dementia, seven patients with Parkinson's disease, and six paired nondemented elderly control individuals. In controls and non-AD patients, a constant expression of trkAII transcripts was detected within all striatum parts. In AD patients, a heterogeneous decrease in trkAII expression was observed in the caudate, putamen, and ventral striatum, resulting either in a drop of trkAII transcript levels or in a weak coamplification of trkAII and trkAI transcripts. The alteration of TrkAII gene expression paralleled those of choline acetyltransferase. Together with previous data, this suggests that the alteration of trk gene expression could contribute to a decrease in NGF binding sites and its protective effects on cholinergic neurons of AD patients.
TrkAII酪氨酸激酶受体与TrkAI亚型的不同之处在于其细胞外结构域插入了六个氨基酸。我们使用逆转录聚合酶链反应（RT-PCR）来确定它们在大鼠和人类大脑中的各自分布。在大鼠的12个脑区中仅检测到trkAII转录本，而在小脑和垂体中同时检测到trkAI和trkAII转录本。在人类中，在额叶、颞叶、枕叶皮质和丘脑中同时检测到trkAI和trkAII转录本，而在海马体和小脑中仅检测到trkAI转录本。在尾状核和壳核中，仅检测到trkAII转录本。此后，我们研究了五名阿尔茨海默病（AD）患者、四名非AD痴呆患者、七名帕金森病患者以及六名配对的非痴呆老年对照个体纹状体中TrkA亚型的表达。在对照组和非AD患者中，在所有纹状体部分均检测到trkAII转录本的恒定表达。在AD患者中，在尾状核、壳核和腹侧纹状体中观察到trkAII表达的异质性降低，导致trkAII转录本水平下降或trkAII与trkAI转录本的弱共扩增。TrkAII基因表达的改变与胆碱乙酰转移酶的改变平行。与先前的数据一起，这表明trk基因表达的改变可能导致AD患者神经生长因子（NGF）结合位点减少及其对胆碱能神经元的保护作用降低。
