The effect of intrastriatal single injection of GDNF on the nigrostriatal dopaminergic system in hemiparkinsonian rats: behavioral and histological studies using two different dosages.
Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-beta superfamily and acts as a neurotrophic factor for the nigrostriatal dopamine (DA) system. Although previous studies have shown that pretreatment with GDNF could prevent degenerative changes of nigrostriatal DA system by DA neurotoxin 6-hydroxydopamine (6-OHDA), it is not really known whether GDNF can induce recovery of nigrostriatal DA system after partial lesioning by 6-OHDA. Substantia nigra has been commonly chosen as injection site for GDNF but a limited number of studies have used striatum as injection site where neural transplantation is commonly performed. Unilateral intrastriatal administration of 6-OHDA was performed in Sprague-Dawley rats to create partial lesion of the nigrostriatal DA system. These hemiparkinsonian model rats received a 10- or 100-microg single injection of human recombinant GDNF into the same portion of the striatum 4 weeks after 6-OHDA treatment. Both animals that received a 10- or 100-microg single injection of GDNF showed decreased apomorphine-induced rotation at 2 weeks after injection. More potent and prolonged functional recovery was observed in animals receiving 100 microg of GDNF than in those receiving 10 microg of GDNF. Tyrosine hydroxylase (TH) immunocytochemistry revealed that TH positive DA fiber density in the striatum and the number of DA cell bodies in the substantia nigra were greater in animals receiving 10 or 100 microg of GDNF than those receiving saline. These immunocytochemical results have also shown that 100 microg of GDNF was more potent than 10 microg of GDNF. These morphological and functional results indicate that GDNF treatment 4 weeks after 6-OHDA lesioning could induce recovery of nigrostriatal DA system. Striatum was a good site for GDNF administration for hemiparkinsonian rats and a single injection of 100 microg of GDNF was more potent than 10 microg of GDNF.
Aoi
M
M
Department of Neurological Surgery, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama, Japan.
Date
I
I
Tomita
S
S
Ohmoto
T
T
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001369:Axons / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007839:Functional Laterality; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007150:Immunohistochemistry; D009068:Movement / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects* / Q000473:pathology*; D009410:Nerve Degeneration / Q000188:drug therapy; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology*; D013565:Sympatholytics / Q000494:pharmacology; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects
D018491:Dopamine Agonists; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D013565:Sympatholytics; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; D004298:Dopamine