Regional Differences in Responsiveness of Adult CNS Axons to Grafts of Cells Expressing Human Neurotrophin 3

Neurotrophin 3 (NT3) belongs to the neurotrophin family, which also includes nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 4/5. NT3 mRNA is widely expressed in the rodent nervous system, but the physiological function of the native protein is still unclear. Genetically mod...

Full description

Saved in:

Bibliographic Details
Published in:	Experimental neurology Vol. 135; no. 1; pp. 36 - 55
Main Authors:	Senut, M-C., Tuszynski, M.H., Raymon, H.K., Suhr, S.T., Liou, N.H., Jones, K.R., Reichardt, L.F., Gage, F.H.
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Inc 01-09-1995 Elsevier
Subjects:	Animals Base Sequence Biological and medical sciences Brain - metabolism Brain - physiology Female Fibroblasts - physiology Fibroblasts - transplantation Ganglia, Sympathetic - metabolism Ganglia, Sympathetic - physiology Hippocampus - metabolism Hippocampus - physiology Humans Locus Coeruleus - metabolism Locus Coeruleus - physiology Medical sciences Molecular Probes Molecular Sequence Data Nerve Growth Factors - genetics Neurosurgery Neurotrophin 3 Rats RNA, Messenger - metabolism Skull, brain, vascular surgery Spinal Cord - metabolism Spinal Cord - physiology Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Spinal cord Rat Rodentia Central nervous system Gene expression Survival Vertebrata Mammalia Messenger RNA Adult animal Graft Fibroblast Graft surgical Brain (vertebrata)
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Neurotrophin 3 (NT3) belongs to the neurotrophin family, which also includes nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 4/5. NT3 mRNA is widely expressed in the rodent nervous system, but the physiological function of the native protein is still unclear. Genetically modified cell lines that produce physiological amounts of NT3 can provide a useful tool in the elucidation of the NT3 effects in the adult central nervous system (CNS). Genetically modified rat primary skin fibroblasts expressing and secreting human NT3 (hNT3) were prepared and characterized. In vitro, cell lines derived from different retroviral constructs expressed hNT3 mRNA, as determined by PCR and RNA blot analysis. Secretion of biologically active hNT3 was confirmed by specific elicitation of neurite outgrowth from cultured chick primary sympathetic and sensory neurons and from rat fetal locus coeruleus neurons in the presence of hNT3-producing cell conditioned media. In vivo, implanted fibroblasts survived well up to the maximal experimental time points of 6 weeks (brain) and 4 weeks (spinal cord) and continued to express hNT3 mRNA in vivo. As early as 2 weeks postgrafting, specific sprouting of host sensory neurites in response to hNT3-producing grafts was observed in the spinal cord. In contrast, hNT3-producing cerebral grafts did not induce a sprouting response different from that observed with control grafts. These findings establish the existence of a regionally different responsiveness of the CNS axons to local hNT3 overexpression.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0014-4886 1090-2430
DOI:	10.1006/exnr.1995.1064