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Journal of Neuroscience, Vol 15, 4223-4237, Copyright © 1995 by Society for Neuroscience
Neurotrophins and the neuroendocrine brain: different neurotrophins sustain anatomically and functionally segregated subsets of hypothalamic dopaminergic neurons
K Berg-von der Emde, WL Dees, JK Hiney, DF Hill, GA Dissen, ME Costa, M Moholt- Siebert and SR Ojeda
Division of Neuroscience, Oregon Regional Primate Research Center- Oregon Health Sciences University, Beaverton 97006, USA.
Hypothalamic neurons control a variety of important hormonal and behavioral
functions. Little is known, however, about the neurotrophic factors that
these neurons may require for survival and/or maintenance of their
differentiated functions. We conducted experiments to examine this issue,
utilizing a combination of immunohistochemical, in situ hybridization and
cell culture approaches. We found that the low affinity receptor for nerve
growth factor (p75 NGFR) is present in small subsets of hypothalamic
peptidergic neurons identified as such by their content of galanin,
luteinizing hormone-releasing hormone (LHRH) and vasointestinal peptide
(VIP). More prominently, however, examination of hypothalamic dopaminergic
(DA) neurons for the presence of p75 NGFR-like immunoreactivity revealed
that the receptor was present on tyrosine hydroxylase (TH)-positive neurons
of the zona incerta and periventricular region, but not on neuroendocrine
DA neurons of the tuberoinfundibular region. In situ hybridization
experiments using a p75 NGFR cRNA confirmed this distribution. Regardless
of the presence or absence of p75 NGFR, neither DA group expresses trkA
mRNA, indicating that these two major hypothalamic subsets of DNA neurons
are NGF-insensitive. A substantial fraction of TH mRNA-positive cells in
the zona incerta expresses trkB mRNA, which encodes the receptor for brain
derived neurotrophic factor (BDNF); in turn BDNF supports the in vitro
survival of hypothalamic TH neurons bearing p75-NGFR, suggesting that BDNF
is trophic for DNA neurons of the zona incerta. In contrast,
tuberoinfundibular DA neurons do not express trkB mRNA, but some have trkC
mRNA, which encodes the receptor for neurotrophin-3 (NT-3). The in vitro
survival of TH neurons devoid of p75-NGFR is supported by NT-3, implying
that NT-3 may be trophic for a subset of tuberoinfundibular DA neurons.
These results suggest that, in spite of expressing an identical
neurotransmitter phenotype, anatomically and functionally segregated DA
neurons of the neurodendocrine brain are sustained by different
neurotrophic factors.
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