Abstract
Parkinson's disease (PD) is characterized by degeneration of nigrostriatal dopaminergic neuronal systems. Several therapeutic tools for PD include medication using l-DOPA and surgeries such as deep brain stimulation are established. However, the therapies are considered as symptomatic therapy, but not basic remedy for PD and a new regenerative therapy would be desired to explore. In this study, the neuroprotective/rescue effects of erythropoietin (EPO), a well known hematopoietic hormone, on dopaminergic neurons were explored with neurogeneic potencies of EPO. EPO (100 IU/day) was continuously administered with micro-osmotic pump for a week to PD model of rats induced by intrastriatal 6-hydroxydopamine (6-OHDA) injection with subsequent behavioral and immunohistochemical investigations. The number of amphetamine-induced rotations of EPO-treated rats significantly decreased, compared to the control rats. The preservation of dopaminergic neurons of EPO-treated rats were confirmed by tyrosine hydroxylase staining and Fluoro-Gold staining. The number of bromodeoxyuridine (BrdU)/polysialic acid-neural cell adhesion molecule (PSA-NCAM) double positive cells in the subventricular zone of EPO-treated rats significantly increased with migratory potencies to the damaged striatum, compared to the control rats. Furthermore, TUNEL staining and phosphorylated Akt staining revealed that the neuroprotective/rescue effects of EPO might be mediated by anti-apoptotic effects through the increase of phosphorylated Akt. These results suggest that continuous low dose infusion of EPO exerts neuroprotective/rescue effects with neurogeneic potentials. EPO might be a strong tool for PD therapy, although the further experiments should be added.
| Original language | English |
|---|---|
| Pages (from-to) | 120-127 |
| Number of pages | 8 |
| Journal | Brain Research |
| Volume | 1254 |
| DOIs | |
| Publication status | Published - Feb 13 2009 |
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Keywords
- 6-OHDA
- Apoptosis
- Dopaminergic neuron
- Neurogenesis
- Subventricular zone
ASJC Scopus subject areas
- Neuroscience(all)
- Clinical Neurology
- Developmental Biology
- Molecular Biology
Cite this
Continuous intraventricular infusion of erythropoietin exerts neuroprotective/rescue effects upon Parkinson's disease model of rats with enhanced neurogenesis. / Kadota, Tomohito; Shingo, Tetsuro; Yasuhara, Takao; Tajiri, Naoki; Kondo, Akihiko; Morimoto, Takamasa; Yuan, Wen Ji; Wang, Feifei; Baba, Tanefumi; Tokunaga, Koji; Date, Yasuyuki Miyoshi, Isao.
In: Brain Research, Vol. 1254, 13.02.2009, p. 120-127.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Continuous intraventricular infusion of erythropoietin exerts neuroprotective/rescue effects upon Parkinson's disease model of rats with enhanced neurogenesis
AU - Kadota, Tomohito
AU - Shingo, Tetsuro
AU - Yasuhara, Takao
AU - Tajiri, Naoki
AU - Kondo, Akihiko
AU - Morimoto, Takamasa
AU - Yuan, Wen Ji
AU - Wang, Feifei
AU - Baba, Tanefumi
AU - Tokunaga, Koji
AU - Date, Yasuyuki Miyoshi, Isao
PY - 2009/2/13
Y1 - 2009/2/13
N2 - Parkinson's disease (PD) is characterized by degeneration of nigrostriatal dopaminergic neuronal systems. Several therapeutic tools for PD include medication using l-DOPA and surgeries such as deep brain stimulation are established. However, the therapies are considered as symptomatic therapy, but not basic remedy for PD and a new regenerative therapy would be desired to explore. In this study, the neuroprotective/rescue effects of erythropoietin (EPO), a well known hematopoietic hormone, on dopaminergic neurons were explored with neurogeneic potencies of EPO. EPO (100 IU/day) was continuously administered with micro-osmotic pump for a week to PD model of rats induced by intrastriatal 6-hydroxydopamine (6-OHDA) injection with subsequent behavioral and immunohistochemical investigations. The number of amphetamine-induced rotations of EPO-treated rats significantly decreased, compared to the control rats. The preservation of dopaminergic neurons of EPO-treated rats were confirmed by tyrosine hydroxylase staining and Fluoro-Gold staining. The number of bromodeoxyuridine (BrdU)/polysialic acid-neural cell adhesion molecule (PSA-NCAM) double positive cells in the subventricular zone of EPO-treated rats significantly increased with migratory potencies to the damaged striatum, compared to the control rats. Furthermore, TUNEL staining and phosphorylated Akt staining revealed that the neuroprotective/rescue effects of EPO might be mediated by anti-apoptotic effects through the increase of phosphorylated Akt. These results suggest that continuous low dose infusion of EPO exerts neuroprotective/rescue effects with neurogeneic potentials. EPO might be a strong tool for PD therapy, although the further experiments should be added.
AB - Parkinson's disease (PD) is characterized by degeneration of nigrostriatal dopaminergic neuronal systems. Several therapeutic tools for PD include medication using l-DOPA and surgeries such as deep brain stimulation are established. However, the therapies are considered as symptomatic therapy, but not basic remedy for PD and a new regenerative therapy would be desired to explore. In this study, the neuroprotective/rescue effects of erythropoietin (EPO), a well known hematopoietic hormone, on dopaminergic neurons were explored with neurogeneic potencies of EPO. EPO (100 IU/day) was continuously administered with micro-osmotic pump for a week to PD model of rats induced by intrastriatal 6-hydroxydopamine (6-OHDA) injection with subsequent behavioral and immunohistochemical investigations. The number of amphetamine-induced rotations of EPO-treated rats significantly decreased, compared to the control rats. The preservation of dopaminergic neurons of EPO-treated rats were confirmed by tyrosine hydroxylase staining and Fluoro-Gold staining. The number of bromodeoxyuridine (BrdU)/polysialic acid-neural cell adhesion molecule (PSA-NCAM) double positive cells in the subventricular zone of EPO-treated rats significantly increased with migratory potencies to the damaged striatum, compared to the control rats. Furthermore, TUNEL staining and phosphorylated Akt staining revealed that the neuroprotective/rescue effects of EPO might be mediated by anti-apoptotic effects through the increase of phosphorylated Akt. These results suggest that continuous low dose infusion of EPO exerts neuroprotective/rescue effects with neurogeneic potentials. EPO might be a strong tool for PD therapy, although the further experiments should be added.
KW - 6-OHDA
KW - Apoptosis
KW - Dopaminergic neuron
KW - Neurogenesis
KW - Subventricular zone
UR - http://www.scopus.com/inward/record.url?scp=58549083938&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=58549083938&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2008.11.094
DO - 10.1016/j.brainres.2008.11.094
M3 - Article
C2 - 19101524
AN - SCOPUS:58549083938
VL - 1254
SP - 120
EP - 127
JO - Brain Research
JF - Brain Research
SN - 0006-8993
ER -