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Gewählte Publikation:

Holm, PC; Rodríguez, FJ; Kresse, A; Canals, JM; Silos-Santiago, I; Arenas, E.
Crucial role of TrkB ligands in the survival and phenotypic differentiation of developing locus coeruleus noradrenergic neurons.
Development. 2003; 130(15): 3535-3545. [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Kresse Adelheid
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Abstract:
The role of glial cell-line derived neurotrophic factor (GDNF) and neurotrophins in the development of locus coeruleus noradrenergic neurons was evaluated. We found that two neurotrophic factors previously reported to prevent the degeneration of lesioned adult central noradrenergic neurons, GDNF and neurotrophin 3 (NT3), do not play significant roles in the prenatal development of locus coeruleus noradrenergic neurons, as demonstrated by: (1) the lack of alterations in double Gdnf/Nt3 null mutant mice; and (2) the lack of survival-promoting effects of GDNF and/or NT3 in rat E13.5 primary cultures. In contrast, null mutant mice for TrkB, the tyrosine kinase receptor for brain-derived neurotrophic factor and neurotrophin 4, displayed a clear loss of locus coeruleus noradrenergic neurons. In accordance with this, treatment of rat E13.5 primary cultures with TrkB ligands prevented the early loss of noradrenergic neurons and maintained their survival for up to 6 days in vitro. Moreover, an additional 5-10-fold increase in the number of tyrosine hydroxylase positive noradrenergic neurons was detected after 12 hours in culture. This second effect of TrkB ligands involved neither proliferation nor survival, because the number of BrdU- or TUNEL-positive noradrenergic neurons did not change and the effect was elicited by delayed administration of either factor. Because TrkB ligands increased the number of tyrosine hydroxylase-positive cells expressing Phox2a, a paired homeodomain protein required for the development of locus coeruleus noradrenergic neurons, but did not affect the number of Phox2a-positive tyrosine hydroxylase-negative cells, our results suggest that the second effect of TrkB ligands may involve promoting or inducing a noradrenergic phenotype. In summary, our findings suggest that, unlike NT3 and GDNF, TrkB ligands are required and sufficient to promote the development of central noradrenergic neurons.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Gene Expression Regulation, Developmental - physiology
Glial Cell Line-Derived Neurotrophic Factor - physiology
Glial Cell Line-Derived Neurotrophic Factor Receptors - physiology
Ligands - physiology
Locus Coeruleus - embryology
Membrane Glycoproteins - metabolism
Mice - metabolism
Mutation - metabolism
Nerve Growth Factors - genetics
Neurons - metabolism
Protein-Tyrosine Kinases - metabolism
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-ret - metabolism
Receptor Protein-Tyrosine Kinases - metabolism
Receptor, trkB - metabolism
Receptor, trkC - metabolism

Find related publications in this database (Keywords)
TrkB
TrkC
BDNF
NT4
NT3
GDNF
locus coeruleus
neurotrophins
rat primary cultures
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