Effect of glial cell line-derived neurotrophic factor (GDNF) co-transplantation with fetal ventral mesencephalic cells (VMC) on functional restoration in 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease: neurobehavioral, neurochemical and immunohistochemical studies.
Among trophic factors already known, glial cell line-derived neurotrophic factor (GDNF) and other members of its family have potent and specific action on dopaminergic neurons. In the present investigation an attempt has been made to validate the role of GDNF co-transplantation with fetal ventral mesencephalic cells (VMC) on functional viability and restoration using neurobehavioral, neurochemical and immunohistochemical parameters at 6 weeks post-transplantation in 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease (PD). A significant restoration (P<0.01) in D-amphetamine induced rotations, spontaneous and apomorphine induced locomotor activity in rats co-transplanted with VMC and GDNF was observed as compared to VMC alone transplanted rats. Level of dopamine (DA), 3,4-dihydroxy-phenyl acetic acid (DOPAC) and dopamine D2 (DA-D2) receptors in the caudate putamen (CPu) were significantly (P<0.001) restored in co-transplanted group as compared to VMC transplanted or GDNF administered animals. The functional viability of transplanted VMC was confirmed by tyrosine hydroxylase (TH) expression and quantification of TH-positive cells by image analysis revealed a significant restoration in TH-IR fibers density as well as TH-IR neurons counts in co-transplanted animals over VMC transplanted animals. Results suggest that co-transplantation of VMC and GDNF may be a better approach towards functional restoration in 6-OHDA lesioned rat model of Parkinson's disease.
Chaturvedi
R K
RK
Developmental Toxicology Division, Industrial Toxicology Research Centre, PO Box 80, M.G. Marg, Lucknow 226 001, India.
Agrawal
A K
AK
Seth
K
K
Shukla
S
S
Chauhan
S
S
Shukla
Y
Y
Sinha
C
C
Seth
P K
PK
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D017024:Chemotherapy, Adjuvant / Q000379:methods; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008124:Locomotion / Q000187:drug effects; D008636:Mesencephalon / Q000637:transplantation*; D009414:Nerve Growth Factors / Q000008:administration & dosage*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000378:metabolism; D020127:Recovery of Function; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D016896:Treatment Outcome
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D016627:Oxidopamine