The differences between high and low-dose administration of VEGF to dopaminergic neurons of in vitro and in vivo Parkinson's disease model

Yasuhara, Takao; Shingo, Tetsuro; Muraoka, Kenichiro; Ji, Yuan; Kameda, Masahiro; Takeuchi, Akihiro; Yano, Akimasa; Nishio, Shinsaku; Matsui, Toshihiro; Miyoshi, Yasuyuki; Hamada, Hirofumi; Date, Isao

doi:10.1016/j.brainres.2004.12.055

Cited by 71 publications

(48 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In patients with Parkinson's disease, side effects of centrally delivered GDNF have been reported (Kordower et al, 1999;Nutt et al, 2003). As we observed in mice transplanted with NPs-AdVEGF, the delivery of low-dose VEGF would be better than a high dose in Parkinson's models (Yasuhara et al, 2005). Therefore, modulation of expression level of growth factors in vivo seems to be very important.…”

Section: Discussionmentioning

confidence: 87%

Growth factor-expressing human neural progenitor cell grafts protect motor neurons but do not ameliorate motor performance and survival in ALS mice

et al. 2009

View full text Add to dashboard Cite

Neural progenitor cells (NPs) have shown several promising benefits for the treatment of neurological disorders. To evaluate the therapeutic potential of human neural progenitor cells (hNPs) in amyotrophic lateral sclerosis (ALS), we transplanted hNPs or growth factor (GF)-expressing hNPs into the central nervous system (CNS) of mutant Cu/Zn superoxide dismutase (SOD1 G93A ) transgenic mice. The hNPs were engineered to express brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), VEGF, neurotrophin-3 (NT-3), or glial cell-derived neurotrophic factor (GDNF), respectively, by adenoviral vector and GDNF by lentiviral vector before transplantation. Donor-derived cells engrafted and migrated into the spinal cord or brain of ALS mice and differentiated into neurons, oligodendrocytes, or glutamate transporter-1 (GLT1)-expressing astrocytes while some cells retained immature markers. Transplantation of GDNF-or IGF-1-expressing hNPs attenuated the loss of motor neurons and induced trophic changes in motor neurons of the spinal cord. However, improvement in motor performance and extension of lifespan were not observed in all hNP transplantation groups compared to vehicle-injected controls. Moreover, the lifespan of GDNF-expressing hNP recipient mice by lentiviral vector was shortened compared to controls, which was largely due to the decreased survival times of female animals. These results imply that although implanted hNPs differentiate into GLT1-expressing astrocytes and secrete GFs, which maintain dying motor neurons, inadequate trophic support could be harmful and there is sexual dimorphism in response to GDNF delivery in ALS mice. Therefore, additional therapeutic approaches may be required for full functional recovery.

show abstract

Section: Discussionmentioning

confidence: 87%

Growth factor-expressing human neural progenitor cell grafts protect motor neurons but do not ameliorate motor performance and survival in ALS mice

et al. 2009

View full text Add to dashboard Cite

show abstract

“…In fact, various factors including GDNF and VEGF have been shown to increase dopaminergic neuronal survival and promote survival and axonal growth in animal models of PD. [9][10][11] In addition to those factors, we and others have reported a potential therapeutic strategy using hepatocyte growth factor (HGF). [12][13][14][15][16][17][18][19] HGF acts as a neurotrophic and survival factor for embryonic motor neurons.…”

Section: Introductionmentioning

confidence: 99%

Prevention of onset of Parkinson’s disease by in vivo gene transfer of human hepatocyte growth factor in rodent model: a model of gene therapy for Parkinson’s disease

et al. 2006

View full text Add to dashboard Cite

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SNi). As neurotrophic factors support the survival and enhance the function of dopaminergic neurons, gene therapy using neurotrophic factors has become the center of interest. Thus, we focused on hepatocyte growth factor (HGF) as a neurotrophic and angiogenic growth factor. At 7 days before injection of 6-hydroxydopamine into the SNi, stereotaxic transfection of human HGF or lacZ plasmid was performed into the unilateral striatum of rats. Expression of human HGF in the injected sites could be detected in rats transfected with HGF plasmid DNA, using immunohistochemical staining. Consistently, human immunoreactive HGF protein could be detected at least up to 12 days after transfection. Interestingly, PD rats transfected with lacZ demonstrated amphetamine-induced rotational asymmetry. However, transfection of HGF plasmid DNA resulted in significant inhibition of abnormal rotation up to 24 weeks in a dose-dependent manner. Over 90% of dopaminergic neurons were lost in PD rats transfected with lacZ, whereas over 70% survived in rats transfected with HGF, as assessed by immunohistochemical staining. Overall, the present study demonstrated that overexpression of HGF prevented neuronal death in a PD rat model, providing a potential novel therapy for PD.

show abstract

“…1). The VEGF concentration has also been found to be important in other biological processes (e.g., neuroprotective effects in dopaminergic neurons [46] and ischemic brain tissue [47]). The concept of dose thresholds is also reflected in other angiogenic growth factors; for example, overexpression of bFGF can cause tumor formation [48].…”

Section: Concentrationmentioning

confidence: 99%

Spatiotemporal control over growth factor signaling for therapeutic neovascularization☆

Cao

Mooney

2007

Advanced Drug Delivery Reviews

109

110

View full text Add to dashboard Cite

Many of the qualitative roles of growth factors involved in neovascularization have been delineated, but it is unclear yet from an engineering perspective how to use these factors as therapies. We propose that an approach that integrates quantitative spatiotemporal measurements of growth factor signaling using 3-D in vitro and in vivo models, mathematic modeling of factor tissue distribution, and new delivery technologies may provide an opportunity to engineer neovascularization on demand.

show abstract

The differences between high and low-dose administration of VEGF to dopaminergic neurons of in vitro and in vivo Parkinson's disease model

Cited by 71 publications

References 29 publications

Growth factor-expressing human neural progenitor cell grafts protect motor neurons but do not ameliorate motor performance and survival in ALS mice

Growth factor-expressing human neural progenitor cell grafts protect motor neurons but do not ameliorate motor performance and survival in ALS mice

Prevention of onset of Parkinson’s disease by in vivo gene transfer of human hepatocyte growth factor in rodent model: a model of gene therapy for Parkinson’s disease

Spatiotemporal control over growth factor signaling for therapeutic neovascularization☆

Contact Info

Product

Resources

About