Protection of nigral neurons by GDNF-engineered marrow cell transplantation

Autor: Martin A. Eglitis, M. Maral Mouradian, Kun Woo Park
Rok vydání: 2001
Předmět:
Male
medicine.medical_specialty
Stromal cell
DNA
Complementary
Tyrosine 3-Monooxygenase
animal diseases
Genetic enhancement
Dopamine
Genetic Vectors
Bone Marrow Cells
Nerve Tissue Proteins
Motor Activity
Transfection
chemistry.chemical_compound
Mice
Parkinsonian Disorders
Neurotrophic factors
Internal medicine
medicine
Glial cell line-derived neurotrophic factor
Animals
Glial Cell Line-Derived Neurotrophic Factor
Nerve Growth Factors
Cells
Cultured
Bone Marrow Transplantation
Neurons
biology
Behavior
Animal
General Neuroscience
MPTP
General Medicine
Genetic Therapy
Recovery of Function
Immunohistochemistry
Transplantation
Mice
Inbred C57BL
Substantia Nigra
medicine.anatomical_structure
Endocrinology
Neuroprotective Agents
nervous system
chemistry
Immunology
biology.protein
Female
Bone marrow
Stem cell
Zdroj: Neuroscience research. 40(4)
ISSN: 0168-0102
Popis: Marrow stromal cells, which have many characteristics of stem cells, populate various non-hematopoietic tissues including the brain. In the present study, the cDNA for the dopaminergic neurotrophic factor Glial Cell Line-Derived Neurotrophic Factor (GDNF) was delivered using marrow cells in the mouse 1-Methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) model of Parkinson's disease. Following cross-sex intravenous bone marrow transplantation with male donor cells that had been transduced with GDNF (GDNF-BMT) or with non-manipulated marrow (Control-BMT), female recipient mice were subjected to systemic MPTP injections. Eight weeks after neurotoxin exposure, more tyrosine hydroxylase immunoreactive nigral neurons and striatal terminal density were observed in the GDNF-BMT mice compared with the Control-BMT group. In addition, following the expected initial behavioral hyperactivity in both groups, a significant difference in motor activity was detected between the two groups. GDNF immunoreactive male donor marrow derived cells were detected in the brains of GDNF-BMT mice but not in controls. These data indicate that marrow derived cells that seed the brain can express biologically active gene products and, therefore, can function as effective vehicles for therapeutic gene transfer to the brain.
Databáze: OpenAIRE
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