Brain-derived neurotrophic factor (BDNF) gene delivery into the CNS using bone marrow cells as vehicles in mice

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is protective in animal models of neurodegenerative diseases. However, BDNF has a short half-life and its efficacy in the CNS when delivered peripherally is limited due to the blood–brain barrier. In the present study, bo...

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Veröffentlicht in:Neuroscience letters 2004-02, Vol.356 (3), p.215-219
Hauptverfasser: Makar, T.K., Trisler, D., Eglitis, M.A., Mouradian, M.M., Dhib-Jalbut, S.
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container_issue 3
container_start_page 215
container_title Neuroscience letters
container_volume 356
creator Makar, T.K.
Trisler, D.
Eglitis, M.A.
Mouradian, M.M.
Dhib-Jalbut, S.
description Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is protective in animal models of neurodegenerative diseases. However, BDNF has a short half-life and its efficacy in the CNS when delivered peripherally is limited due to the blood–brain barrier. In the present study, bone marrow cells were used as vehicles to deliver the BDNF gene into the CNS. Marrow cells obtained from 6 to 8 week-old SJL/J mice were transduced with BDNF expressing pro-virus. RT-PCR analysis revealed that BDNF mRNA was expressed in transduced but not in non-transduced marrow cells. Additionally, virus transduced marrow cells expressed the BDNF protein (296±1.2 unit/ml). BDNF-transduced marrow cells were then transplanted into irradiated mice through the tail vein. Three months post-transplantation, significant increases in BDNF as well as glutamic acid decarboxylase (GAD 67) mRNA were detected in the brains of BDNF transplanted mice compared to untransplanted animals, indicating biological activity of the BDNF transgene. Thus, bone marrow cells can be used as vehicles to deliver the BDNF gene into the brain with implications for the treatment of neurological diseases.
doi_str_mv 10.1016/j.neulet.2003.11.045
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subjects Animals
Biological and medical sciences
Blotting, Northern
Bone marrow cell transplantation
Bone Marrow Cells - metabolism
Bone Marrow Transplantation - methods
Brain-derived neurotrophic factor
Brain-Derived Neurotrophic Factor - genetics
Brain-Derived Neurotrophic Factor - metabolism
Central Nervous System - metabolism
Enzyme-Linked Immunosorbent Assay - methods
Fundamental and applied biological sciences. Psychology
Gene therapy
Gene Transfer Techniques
Glutamate Decarboxylase - genetics
Glutamate Decarboxylase - metabolism
Indoles - metabolism
Isoenzymes - genetics
Isoenzymes - metabolism
Mice
Mice, Inbred Strains
Neurodegeneration
Reverse Transcriptase Polymerase Chain Reaction - methods
RNA, Messenger - biosynthesis
Vertebrates: nervous system and sense organs
title Brain-derived neurotrophic factor (BDNF) gene delivery into the CNS using bone marrow cells as vehicles in mice
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