The effect of glial cell line-derived neurotrophic factor in fibrin glue on developing dopamine neurons.
Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-beta superfamily, promotes the survival, morphological differentiation, and high-affinity dopamine (DA) uptake of cultured nigral DA neurons. In order to test potential methodology for peptide delivery in vivo, GDNF-containing fibrin glue balls (8 micrograms/ball) were incorporated with pieces of fetal ventral mesencephalon (E15) and transplanted into the anterior chambers of sympathetically denervated adult rats. Five weeks after grafting, the numbers of TH-positive neurons and the nerve fiber density were significantly higher in the ventral mesencephalic grafts treated with GDNF-containing glue balls than in those treated with vehicle. In addition, the laminin and GFAP immunoreactivities were similar between the two groups. These data support the concept that GDNF is a potent trophic factor for DA neurons in vivo and suggest that fibrin glue may provide a unique and safe means to permit prolonged delivery of trophic molecules to CNS tissues.
Cheng
H
H
Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.
Hoffer
B
B
Strömberg
I
I
Russell
D
D
Olson
L
L
D000818:Animals; D016380:Brain Tissue Transplantation; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism*; D015718:Fibrin Tissue Adhesive / Q000494:pharmacology*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006133:Growth Substances; D007150:Immunohistochemistry; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011995:Recombination, Genetic; D013378:Substantia Nigra / Q000378:metabolism
D015718:Fibrin Tissue Adhesive; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006133:Growth Substances; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D004298:Dopamine