Effect of intranigral injection of GDNF and EGF on the survival and possible differentiation fate of progenitors and immature neurons in 6-OHDA-lesioned rats.
We investigated the survival and the possible differentiation fate of the progenitors and immature neurons in the pars compacta of the substantia nigra (SNc) by intranigral injection of a glial cell line-derived neurotropic factor (GDNF) or glial cell line-derived neurotropic factor plus epidermal growth factor (EGF + GDNF) in 6-hydroxydopamine (6-OHDA)-lesioned rats. First, we performed behavioral tests by postural asymmetry and forelimb akinesia on the rats injected with 6-OHDA in striatumat day 7, and selected the qualified model according to the results. Then, intranigral GDNF or EGF + GDNF treatment was administered in the qualified PD model rats. On day 21, behavioral tests were performed with these rats; and then the rats were sacrificed for analyses of β-tubulin isotype-III (Tuj1), nestin, glial fibrillary acidic protein (GFAP), and tyrosine hydroxylase (TH) by immunohistochemistry and Western blotting. The results indicated that GDNF could promote the survival of the progenitor cells and immature neurons in rat SNc following 6-OHDA lesion. Moreover, EGF is capable of enhancing the survival effect of GDNF on the progenitor cells and immature neurons in SNc. On day 21, rapid functional recovery from the lesion-induced behavioral asymmetries was observed in the GDNF or EGF + GDNF treated rats, and the numbers of TH-positive neurons increased in SNc, suggesting that the rats might generate new dopaminergic neurons. Thus, our study provides the new insight that the progenitors and immature neurons in SNc of 6-OHDA-lesioned rats might be able to differentiate toward the dopaminergic neurons fate subsequent to treatment with GDNF or EGF + GDNF.
Yu
Zheng-Quan
ZQ
Department of Neurosurgery, Xuzhou Medical College, 221002 Xuzhou, People's Republic of China.
Zha
Ji-Hui
JH
Liu
Hong-Mei
HM
Ding
Yan-Xia
YX
Wang
Yan-Qian
YQ
Wang
Hong-Jun
HJ
Gao
Dian-Shuai
DS
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002454:Cell Differentiation; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D008297:Male; D058953:Neural Stem Cells; D009474:Neurons / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D014404:Tubulin / Q000378:metabolism
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D014404:Tubulin; D004815:Epidermal Growth Factor; D016627:Oxidopamine