title: Expression of full-length and truncated trkB in human striatum and substantia nigra neurons: implications for Parkinson's disease.
abstract: Brain derived neurotrophic factor (BDNF) is a potent mediator of cell survival and differentiation and can reverse neuronal injury associated with Parkinson's disease (PD). Tropomyosin receptor kinase B (trkB) is the high affinity receptor for BDNF. There are two major trkB isoforms, the full-length receptor (trkB.tk(+)) and the truncated receptor (trkB.t1), that mediate the diverse, region specific functions of BDNF. Both trkB isoforms are widely distributed throughout the brain, but the isoform specific distribution of trkB.t1 and trkB.tk(+) to human neurons is not well characterized. Therefore, we report the regional and neuronal distribution of trkB.tk(+) and trkB.t1 in the striatum and substantia nigra pars compacta (SNpc) of human autopsy tissues from control and PD cases. In both PD and control tissues, we found abundant, punctate distribution of trkB.tk(+) and trkB.t1 proteins in striatum and SNpc neurons. In PD, trkB.tk(+) is decreased in striatal neurites, increased in striatal somata, decreased in SNpc somata and dendrites, and increased in SNpc axons. TrkB.t1 is increased in striatal somata, decreased in striatal axons, and increased in SNpc distal dendrites. We believe changes in trkB isoform distribution and expression levels may be markers of pathology and affect the neuronal response to BDNF.
authors.affiliation: , Forty Fort, PA, 18704, USA.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Fenner
authors.forename: Cristian L
authors.initials: CL
authors.lastname: Achim
authors.forename: Barbara Murray
authors.initials: BM
authors.lastname: Fenner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; D013378:Substantia Nigra / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D020033:Protein Isoforms; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; C000591259:tropomyosin-related kinase-B, human