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, 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.
Makar
T K
TK
Department of Neurology, University of Maryland, Baltimore 21201, USA.
Trisler
D
D
Eglitis
M A
MA
Mouradian
M M
MM
Dhib-Jalbut
S
S
D000818:Animals; D015152:Blotting, Northern; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018014:Gene Transfer Techniques; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D019208:Brain-Derived Neurotrophic Factor; D007211:Indoles; D007527:Isoenzymes; D012333:RNA, Messenger; C007293:DAPI; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1