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BDNF gene transfer ...
BDNF gene transfer to the mammalian brain using CNS-derived neural precursors
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- Rubio, F. T. (författare)
- Autonomous University of Madrid
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- Kokaia, Z. (författare)
- Lund University,Lunds universitet,Stem Cells & Restorative Neurology,Forskargrupper vid Lunds universitet,Lund University Research Groups
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- Del Arco, A. (författare)
- Autonomous University of Madrid
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- García-Simón, M. I. (författare)
- Autonomous University of Madrid
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- Snyder, E. Y. (författare)
- Boston Children's Hospital
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- Lindvall, O. (författare)
- Lund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Satrústegui, J. (författare)
- Autonomous University of Madrid
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- Martínez-Serrano, A. (författare)
- Autonomous University of Madrid
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(creator_code:org_t)
- 1999-11-16
- 1999
- Engelska 16 s.
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Ingår i: Gene Therapy. - : Springer Science and Business Media LLC. - 0969-7128 .- 1476-5462. ; 6:11, s. 1851-1866
- Relaterad länk:
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http://dx.doi.org/10...
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https://www.nature.c...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Neural stem cell lines represent a homogeneous source of cells for genetic, developmental, and gene transfer and repair studies in the nervous system. Since both gene transfer of neurotrophic factors and cell replacement strategies are of immediate interest for therapeutical purposes, we have generated BDNF-secreting neural stem cell lines and investigated to what extent different endogenous levels of BDNF expression affect in vitro survival, proliferation and differentiation of these cells. Also we have investigated the in vivo effects of such BDNF gene transfer procedure in the rat neostriatum. Hippocampus- and cerebellum-derived cell lines reacted differently to manipulations aimed at varying their levels of BDNF production. Overexpression of BDNF enhanced survival of both cell types, in a serum-deprivation assay. Conversely, and ruling out unspecific effects, expression of an antisense version of BDNF resulted in compromised survival of cerebellum-derived cells, and in a lethal phenotype in hippocampal progenitors. These data indicate that endogenous BDNF level strongly influences the in vitro survival of these cells. These effects are more pronounced for hippocampus- than for cerebellum-derived progenitors. Hippocampus-derived BDNF overproducers showed no major change in their capacity to differentiate towards a neuronal phenotype in vitro. In contrast cerebellar progenitors overproducing BDNF did not differentiate into neurons, whereas cells expressing the antisense BDNF construct generated cells with morphological features of neurons and expressing immunological neuronal markers. Taken together these results provide evidence that BDNF controls both the in vitro survival and differentiation of neural stem cells. After in vivo transplantation of BDNF-overproducing cells to the rat neostriatum, these survived better than the control ones, and induced the expected neurotrophic effects on cholinergic neurons. However, long-term (3 months) administration of BDNF resulted in detrimental effects, at this location. These findings may be of importance for the understanding of brain development, for the design of therapeutic neuro-regenerative strategies, and for cell replacement and gene therapy studies.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Brain repair
- Development
- Gene therapy
- Gene transfer
- Neurotrophin
- Transplantation
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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