Regulation of neuropeptide expression in the brain by neurotrophins |
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Authors: | Josette Carnahan Hiroyuki Nawa |
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Institution: | (1) Amgen Center, Neuroscience Division, 91320 Thousand Oaks, CA;(2) Beckman Neuroscience Center, Cold Spring Harbor Laboratory, 1 Bungtown Road, 11724 Cold Spring Harbor, NY |
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Abstract: | Neurotrophins, which are structurally related to nerve growth factor, have been shown to promote survival of various neurons.
Recently, we found a novel activity of a neurotrophin in the brain: Brain-derived neurotrophic factor (BDNF) enhances expression
of various neuropeptides. The neuropeptide differentiation activity was then compared among neurotrophins both in vivo and
in vitro. In cultured neocortical neurons, BDNF and neurotrophin-5 (NT-5) remarkably increased levels of neuropeptide Y and
somatostatin, and neurotrophin-3 (NT-3) also increased these peptides but required higher concentrations. At elevating substance
P, however, NT-3 was as potent as BDNF. In contrast, NGF had negligible or no effect. Neurotrophins administered into neonatal
brain exhibited slightly different potencies for increasing these neuropeptides: The most marked increase in neuropeptide
Y levels was obtained in the neocortex by NT-5, whereas in the striatum and hippocampus by BDNF, although all three neurotrophins
increased somatostatin similarly in all the brain regions examined. Overall spatial patterns of the neuropeptide induction
were similar among the neurotrophins. Neurons in adult rat brain can also react with the neurotrophins and alter neuropeptide
expression in a slightly different fashion. Excitatory neuronal activity and hormones are known to change expression of neurotrophins.
Therefore, neurotrophins, neuronal activity, and hormones influence each other and all regulate neurotransmitter/peptide expression
in developing and mature brain. Physiological implication of the neurotransmitter/peptide differentiation activities is also
discussed. |
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Keywords: | Nerve growth factor brain-derived neurotrophic factor neurotrophin neuropeptide Y somatostatin substance P neocortex striatum hippocampus seizure plasticity |
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