Expression of Trk isoforms in brain regions and in the striatum of patients with Alzheimer's disease.
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.
Dubus
P
P
Laboratoire d'Histologie-Embryologie, EA 2406 Université de Bordeaux 2, Bordeaux Cedex, 33076, France.
Faucheux
B
B
Boissière
F
F
Groppi
A
A
Vital
C
C
Vital
A
A
Agid
Y
Y
Hirsch
E C
EC
Merlio
J P
JP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020917:Receptor, trkA / Q000378:metabolism*; D020813:Receptor, trkB / Q000378:metabolism
D020033:Protein Isoforms; D020917:Receptor, trkA; D020813:Receptor, trkB