Single administration of GDNF into the striatum induced protection
and repair of the nigrostriatal dopaminergic system in the intrastriatal
6-hydroxydopamine injection model of hemiparkinsonism
Affiliations: Department of Neurological Surgery, Okayama University
Medical School, Okayama 700-8558, Japan
Note: [] Correspondence to: Isao Date, M.D., Department of Neurological
Surgery, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama
700-8558, Japan. Tel.: +81 86 235 7336; Fax: +81 86 227 0191; E-mail:
[email protected]
Abstract: Purpose: Neurotrophic factor delivery into the brain is a promising
approach in the treatment of Parkinson's disease. Glial cell line-derived
neurotrophic factor (GDNF) is one of the most potent neurotrophic factors for
dopaminergic neurons. Although multiple injections of GDNF into the brain are
commonly performed in experimental studies, the present study investigates the
efficacy of using a single injection of GDNF, which may be useful in elinically
applying this treatment. Methods: Unilateral 6-hydroxydoparnine (6-OHDA)
administration into the striatum was perforrned in Sprague-Dawley rats to
create a partial lesion of the nigrostriatal DA system. These parkinsonian
model rats received a single injection of human recombinant GDNF into the same
portion of the striatum either 24 h before or 4 weeks after 6-OHDA treatrnent.
Results: GDNF injected into the striatum before 6-OHDA administration potently
protected the dopaminergic system, as shown by the numbers of mesencephalic
dopaminergie neuron cell bodies and dopaminergic nerve terminal densities in
the striatum. Dopaminergic neuron cell bodies and fiber densities were also
significantly restored when GDNF was given after 6-OHDA administration,
although the degree of restoration was lower than in the protective experiment.
ODNF administration ameliorated apomorphine-induced rotational behavior in
animals receiving it either before or after 6-OHDA treatment. However, the
degree of improvement was less prominent when GDNF was iniected after 6-OHDA.
Conclusion: Intracerebral GDNF adininistration exerts both protective and
regenerative effects on the nigrostriatal dopaminergic system, a finding which
may have implications for the development of new treatment strategies for
Parkinson's disease.
