Mobilization of neural stem cells and generation of new neurons in 6-OHDA-lesioned rats by intracerebroventricular infusion of liver growth factor.
Neural stem cells with self-renewal and multilineage potential persist in the subventricular zone of the adult mammalian forebrain. These cells remain relatively quiescent but, under certain conditions, can be stimulated, giving rise to new neurons. Liver growth factor (LGF) is a mitogen for liver cells that shows biological activity in extrahepatic sites and is useful for neuroregenerative therapies. The aim of this study was to investigate the potential neurogenic activity of LGF in the 6-hydroxydopamine rat model of Parkinson's disease. Proliferation was significantly increased in the subventricular zone and denervated striatum of rats receiving ICV LGF infusions, and 25% of the proliferating cells were doublecortin-positive neurons. Doublecortin-positive cells with the morphology of migrating neuroblasts were also observed in the dorsal and ventral regions of the striatum of LGF-infused animals. Moreover, some newly generated cells were neuronal nuclei-positive mature neurons. LGF also stimulated microglia and induced astrogliosis, both phenomena associated with generation and migration of new neurons in the adult brain. In summary, our study shows that LGF stimulates neurogenesis when applied intraventricularly in 6-hydroxydopamine-lesioned rats. Considering that this factor also promotes neuronal migration into damaged tissue, we propose LGF as a novel factor useful for neuronal replacement in neurodegenerative diseases.
Gonzalo-Gobernado
Rafael
R
Servicio de Neurobiología, Hospital Ramón y Cajal, Carretera de Colmenar Km. 9.1, 28034 Madrid, Spain.
Reimers
Diana
D
Herranz
Antonio S
AS
Díaz-Gil
Juan José
JJ
Osuna
Cristina
C
Asensio
María José
MJ
Baena
Silvia
S
Rodríguez-Serrano
Macarena
M
Bazán
Eulalia
E
D000818:Animals; D001663:Bilirubin / Q000008:administration & dosage / Q000494:pharmacology*; D002465:Cell Movement; D049109:Cell Proliferation; D002552:Cerebral Ventricles / Q000187:drug effects / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D000089662:Doublecortin Protein; D005260:Female; D007276:Injections, Intraventricular; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D008934:Mitogens / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D055495:Neurogenesis; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000008:administration & dosage / Q000494:pharmacology*; D000075462:Serum Albumin, Human; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D008934:Mitogens; D012709:Serum Albumin; C053498:albumin-bilirubin complex; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001663:Bilirubin; D000075462:Serum Albumin, Human