Neurotrophic factor in the treatment of Parkinson disease

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Parkinson disease (PD) is a well-known degenerative disease resulting in the depletion of dopamine-producing neurons in the pars compacta of the substantia nigra. Adenoviral vector delivery of neurotrophic factors may provide a potential therapy for PD. The authors examined whether glial cell line–derived neurotrophic factor (GDNF) delivered via adenoviral vector (Ad-GDNF) could promote functional recovery in a rat model of PD. Additionally, they examined whether neural precursor cells (NPCs) provide the therapeutic potential of cultured neural cells for cell regeneration and replacement in PD.

Methods

All animals underwent stereotactic injection of 6-hydroxydopamine into the right substantia nigra. Eight weeks later, the rats were tested for apomorphine-induced rotational asymmetry and evaluation of explanted grafts infected with the complementary DNA for GDNF containing NPCs and NPCs alone. In the NPC cultures of embryonic rat striata, the authors found that basic fibroblast growth factor induced the proliferation of stem cells, which give rise to spheres of undifferentiated cells that generate neurons and glia.

Conclusions

In this study the authors found that the reduction of apomorphine-induced rotation was more prominent in parkinsonian rats that received Ad-GDNF-treated grafts containing NPCs (61%) than in those that received grafts of NPCs alone (16%).

Abbreviations used in this paper:Ad-GDNF = adenoviral glial cell line–derived neurotrophic factor; bFGF = basic fibroblast growth factor; CMV = cytomegalovirus; CNS = central nervous system; DMEM = Dulbecco modified Eagle's medium; FBS = fetal bovine serum; GFP = green fluorescent protein; IgG = immunoglobulin G; L-DOPA = L-3,4-dihydroxyphenylalanine; NPC = neural precusor cell; PBS = phosphate-buffered saline; PD = Parkinson disease; TH = tyrosine hydroxylase; 6-OHDA = 6-hydroxydopamine.

Object

Parkinson disease (PD) is a well-known degenerative disease resulting in the depletion of dopamine-producing neurons in the pars compacta of the substantia nigra. Adenoviral vector delivery of neurotrophic factors may provide a potential therapy for PD. The authors examined whether glial cell line–derived neurotrophic factor (GDNF) delivered via adenoviral vector (Ad-GDNF) could promote functional recovery in a rat model of PD. Additionally, they examined whether neural precursor cells (NPCs) provide the therapeutic potential of cultured neural cells for cell regeneration and replacement in PD.

Methods

All animals underwent stereotactic injection of 6-hydroxydopamine into the right substantia nigra. Eight weeks later, the rats were tested for apomorphine-induced rotational asymmetry and evaluation of explanted grafts infected with the complementary DNA for GDNF containing NPCs and NPCs alone. In the NPC cultures of embryonic rat striata, the authors found that basic fibroblast growth factor induced the proliferation of stem cells, which give rise to spheres of undifferentiated cells that generate neurons and glia.

Conclusions

In this study the authors found that the reduction of apomorphine-induced rotation was more prominent in parkinsonian rats that received Ad-GDNF-treated grafts containing NPCs (61%) than in those that received grafts of NPCs alone (16%).

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Article Information

Address reprint requests to: Young Mi Yoo, Ph.D., Department of Neurosurgery, Gachon Medical College, Gil Medical Center, 1198 Kuwel-Dong, Namdong-Ku, Inchon 405–220, South Korea. email: neurobeauty@hanmail.net.

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