Platelet-derived growth factor (PDGF-BB) and brain-derived neurotrophic factor (BDNF) induce striatal neurogenesis in adult rats with 6-hydroxydopamine lesions.
The effects of i.c.v. infused platelet-derived growth factor and brain-derived neurotrophic factor on cell genesis, as assessed with bromodeoxyuridine (BrdU) incorporation, were studied in adult rats with unilateral 6-hydroxydopamine lesions. Both growth factors increased the numbers of newly formed cells in the striatum and substantia nigra to an equal extent following 10 days of treatment. At 3 weeks after termination of growth factor treatment, immunostaining of BrdU-labeled cells with the neuronal marker NeuN revealed a significant increase in newly generated neurons in the striatum. In correspondence, many doublecortin-labeled neuroblasts were also observed in the denervated striatum following growth factor treatment. Further evaluation suggested that a subset of these new neurons expresses the early marker for striatal neurons Pbx. However, no BrdU-positive cells were co-labeled with DARPP-32, a protein expressed by mature striatal projection neurons. Both in the striatum and in the substantia nigra there were no indications of any newly born cells differentiating into dopaminergic neurons following growth factor treatment, such that BrdU-labeled cells never co-expressed tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. In conclusion, our results suggest that administration of these growth factors is capable of recruiting new neurons into the striatum of hemiparkinsonian rats.
Mohapel
P
P
Section for Neuronal Survival, Wallenberg Neuroscience Center, BMC A-10, SE-221 84 Lund, Sweden. paul.mohapel@neurol.lu.se
Frielingsdorf
H
H
Häggblad
J
J
Zachrisson
O
O
Brundin
P
P
D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D003342:Corpus Striatum / Q000166:cytology* / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D000089662:Doublecortin Protein; D004333:Drug Administration Routes; D004347:Drug Interactions; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D018613:Microscopy, Confocal / Q000379:methods; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018663:Adrenergic Agents; D019208:Brain-Derived Neurotrophic Factor; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D010982:Platelet-Derived Growth Factor; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001973:Bromodeoxyuridine