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Wirth, MJ; Patz, S; Wahle, P.
Transcellular induction of neuropeptide Y expression by NT4 and BDNF.
Proc Natl Acad Sci U S A. 2005; 102(8):3064-3069 Doi: 10.1073/pnas.0404712102 [OPEN ACCESS]
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Co-Autor*innen der Med Uni Graz
Patz Silke
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Abstract:
The transcellular signaling of neurotrophins is postulated, but evidence is scarce. We now show that a small number of NT4- and BDNF-overexpressing neurons in the cortical explant of thalamocortical cocultures rapidly evoked a Trk receptor-dependent upregulation of neuropeptide Y (NPY) mRNA in interneurons. In contrast to BDNF, the action of NT4 was independent of calcium influx through NMDA receptors and L-type calcium channels. NPY neurons vastly outnumbered the neurotrophin-overexpressing neurons (mostly pyramidal cells), arguing for a spread of the neurotrophin signal via axonally connected neuronal populations. Furthermore, NT4 transfection of one explant of axonally connected corticocortical cocultures evoked significantly larger numbers of NPY neurons in both explants. Delivery of the signal was not by diffusion of neurotrophins via the medium. Moreover, cortical NPY neuron numbers increased after NT4 and BDNF transfection of a cocultured tectal explant innervated selectively by cortical layer V pyramidal neurons. The transcellular induction of NPY suggests a source-to-sink model for axonal transport and a local cortical redistribution of TrkB ligands to interneurons competent for NPY expression.
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Animals -
Brain-Derived Neurotrophic Factor - genetics
Calcium - metabolism
Cerebral Cortex - metabolism
Gene Expression Regulation - metabolism
Nerve Growth Factors - genetics
Neuropeptide Y - genetics
Nifedipine - pharmacology
Protein-Tyrosine Kinases - physiology
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Signal Transduction - physiology

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