Human nerve growth factor: biological and immunological activities, and clinical possibilities in neurodegenerative disease.
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Amino Acid Sequence↗
Biomedical subjects
C Wetmore
Publications and source records attributed to C Wetmore.
The nerve growth factor receptor gene is expressed in both neuronal and non-neuronal tissues in the human fetus.
In situ hybridization was used to study expression of beta-nerve growth factor receptor (NGF-R) mRNA in the early human fetus. In 8- to 12-week old fetuses, high labelling was found over motoneurons along the entire length of the lateral motor column. High levels of NGF-R mRNA were also seen over most developing nerve cell bodies in both the dorsomedial and ventrolateral part of the dorsal root ganglia. Lower, but clearly specific labelling was detected over a subpopulation of cells in Auerbach's plexus in the intestines. Evidence for a non-neuronal expression of NGF-R mRNA came from labelling over a subpopulation of cells in glomeruli of the kidney in a 12-week old human embryo. Myoblasts in skeletal muscle anlagen were labelled as well as cells along peripheral nerve. The widespread expression of NGF-R mRNA in the human fetus suggests that the NGF-R is important for development of a variety of different tissues of both neuronal and non-neuronal origin.
Fetus↗
Localization of brain-derived neurotrophic factor mRNA to neurons in the brain by in situ hybridization.
Brain-derived neurotrophic factor (BDNF) which supports survival of and fiber outgrowth from sensory neurons and retinal ganglion cells has recently been cloned. It is closely related to nerve growth factor (NGF), which we had demonstrated earlier by in situ hybridization to be expressed in the brain by cholinergic target neurons. Using oligonucleotide probes we now describe aspects of the distribution of BDNF mRNA in the adult pig and rat brain. Similar to NGF, BDNF expression in vivo in the central nervous system appeared to be mostly confined to neurons. In the hippocampal formation, strongly labeled neurons were found in and around the pyramidal layer, as well as in the granular layer and the hilus of the dentate gyrus of both pig and rat. Other neurons in these areas were more weakly labeled or unlabeled. High BDNF expression was also shown in scattered neurons in cortex cerebri, in many neurons in claustrum and in certain other areas. These results demonstrate that the similarity in structure between NGF and BDNF is paralleled by a similarity in cellular expression, suggesting that BDNF, like NGF, may act via a direct neuron-to-neuron interaction. It is possible that some neurons, for example, in the hippocampal formation, express both NGF and BDNF. Finally, the localization of BDNF expression in cortical areas and in claustrum suggests that the target neurons for this factor extend beyond the sensory ganglion and retinal ganglion cells.
Animals↗
Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family.
Cells expressing mRNA for hippocampus-derived neurotrophic factor (HDNF/NT-3) or brain-derived neurotrophic factor (BDNF) were identified by in situ hybridization. In the rat brain, HDNF mRNA was predominantly found in pyramidal neurons in CA1 and CA2 of the hippocampus. Lower levels of HDNF mRNA were found in granular neurons of the dentate gyrus and in neurons of the taenia tecta and induseum griseum. BDNF mRNA-expressing cells were more widely distributed in the rat brain, with high levels in neurons of CA2, CA3, and the hilar region of the dentate gyrus, in the external and internal pyramidal layers of the cerebral cortex, in the claustrum, and in one brainstem structure. Lower levels were seen in CA1 and in the granular layer of the hippocampus, in the taenia tecta, and in the mammillary complex. In peripheral tissues, HDNF mRNA was found in glomerular cells in the kidney, secretory cells in the male rat submandibular gland, and epithelial cells in secondary and tertiary follicles in the ovary. Cells expressing BDNF mRNA were found in the dorsal root ganglia, where neurons of various sizes were labeled.
Animals↗