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Glial cell line-derived neurotrophic factor supports survival of injured midbrain dopaminergic neurons.
- Source :
-
The Journal of comparative neurology [J Comp Neurol] 1995 May 15; Vol. 355 (4), pp. 479-89. - Publication Year :
- 1995
-
Abstract
- Glial cell-lined derived neurotrophic factor (GDNF) has been shown to promote survival of developing mesencephalic dopaminergic neurons in vitro. In order to determine if there is a positive effect of GDNF on injured adult midbrain dopaminergic neurons in situ, we have carried out experiments in which a single dose of GDNF was injected into the substantia nigra following a unilateral lesion of the nigrostriatal system. Rats were unilaterally lesioned by a single stereotaxic injection of 6-hydroxydopamine (6-OHDA; 9 micrograms/4 microliters normal saline with 0.02% ascorbate) into the medial forebrain bundle and tested weekly for apomorphine-induced (0.05 mg/kg s.c.) contralateral rotation behavior. Rats that manifested > 300 turns/hour received a nigral injection of 100 micrograms GDNF, or cytochrome C as a control, 4 weeks following the 6-OHDA lesion. Rotation behavior was quantified weekly for 5 weeks after GDNF. Rats were subsequently anesthetized, transcardially perfused, and processed for tyrosine hydroxylase immunohistochemistry. It was found that 100 micrograms GDNF decreased apomorphine-induced rotational behavior by more than 85%. Immunohistochemical studies revealed that tyrosine hydroxylase immunoreactivity was equally reduced in the striatum ipsilateral to the lesion in both cytochrome C and GDNF-injected animals. In contrast, large increments in tyrosine hydroxylase immunoreactivity were observed in the substantia nigra of animals treated with 100 micrograms of GDNF, with a significant increase in numbers of tyrosine hydroxylase-immunoreactive cell bodies and neurites as well as a small increase in the cell body area of these neurons. The results suggest that GDNF can maintain the dopaminergic neuronal phenotype in a number of nigral neurons following a unilateral nigrostriatal lesion in the rat.
- Subjects :
- Animals
Apomorphine
Cell Survival drug effects
Glial Cell Line-Derived Neurotrophic Factor
Image Processing, Computer-Assisted
Immunohistochemistry
Male
Mesencephalon anatomy & histology
Mesencephalon drug effects
Nerve Growth Factors administration & dosage
Nerve Tissue Proteins administration & dosage
Neuronal Plasticity drug effects
Oxidopamine
Rats
Rats, Inbred F344
Stereotyped Behavior drug effects
Tyrosine 3-Monooxygenase metabolism
Dopamine physiology
Mesencephalon cytology
Nerve Growth Factors pharmacology
Nerve Tissue Proteins pharmacology
Neurons drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9967
- Volume :
- 355
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of comparative neurology
- Publication Type :
- Academic Journal
- Accession number :
- 7636027
- Full Text :
- https://doi.org/10.1002/cne.903550402