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Regional differences in responsiveness o ... expressing human neurotrophin 3
Regional differences in responsiveness of adult CNS axons to grafts of cells expressing human neurotrophin 3.
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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.
Senut MC, Tuszynski MH, Raymon HK, Suhr ST, Liou NH, Jones KR, Reichardt LF, Gage FH
Experimental neurology
1995-09-01 00:00
135
1
36-55
Animals,Base Sequence,Brain,Female,Fibroblasts,Ganglia, Sympathetic,Hippocampus,Humans,Locus Coeruleus,Molecular Probes,Molecular Sequence Data,Nerve Growth Factors,Neurotrophin 3,RNA, Messenger,Rats,Spinal Cord,Molecular Probes,Nerve Growth Factors,Neurotrophin 3,RNA, Messenger
Department of Neurosciences, University of California-San Diego, La Jolla 92093-0627, USA
Exp. Neurol.
NIA AG 10435, NIMH MH 48200, FIC TW 04813
0014-4886
10.1006/exnr.1995.1064
S0014-4886(85)71064-3
599
True
7556552
