Publications (3)7.36 Total impact
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Article: Rosiglitazone protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity through inhibition of microglia activation.
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ABSTRACT: Recent evidence has suggested that microglia activation plays an important role in the pathogenesis of Parkinson's disease (PD). Activated microglia secrete various proinflammatory cytokines and neurotoxic mediators, which may contribute to the development of PD. Thus, the inhibition of microglia activation may have a therapeutic benefit in the treatment of PD. In the present study, using mesencephalic neuron-microglia mixed culture and microglia-enriched culture, we investigated whether rosiglitazone (RGZ), a member of peroxisome proliferator-activated receptor gamma (PPARγ) agonists, could inhibit microglia activation. Our results showed that RGZ significantly inhibited lipopolysaccharide (LPS)-induced microglia activation and the production of tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), and superoxide. We further investigated the intracellular signaling pathways regulating the production of TNF-α and NO in LPS-activated microglia. The results showed that RGZ inhibited the phosphorylation and nuclear translocation of the p65 subunit of NF-κB, and the phosphorylation of p38 mitogen-activated protein kinase (p38MAPK). Taken together, our results suggested that the therapeutic effects of RGZ were partially mediated by modulating microglia activation.The International journal of neuroscience 04/2012; 122(9):532-40. · 0.86 Impact Factor -
Article: Dopamine neuron stimulating actions of a GDNF propeptide.
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ABSTRACT: Neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), have shown great promise for protection and restoration of damaged or dying dopamine neurons in animal models and in some Parkinson's disease (PD) clinical trials. However, the delivery of neurotrophic factors to the brain is difficult due to their large size and poor bio-distribution. In addition, developing more efficacious trophic factors is hampered by the difficulty of synthesis and structural modification. Small molecules with neurotrophic actions that are easy to synthesize and modify to improve bioavailability are needed. Here we present the neurobiological actions of dopamine neuron stimulating peptide-11 (DNSP-11), an 11-mer peptide from the proGDNF domain. In vitro, DNSP-11 supports the survival of fetal mesencephalic neurons, increasing both the number of surviving cells and neuritic outgrowth. In MN9D cells, DNSP-11 protects against dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA)-induced cell death, significantly decreasing TUNEL-positive cells and levels of caspase-3 activity. In vivo, a single injection of DNSP-11 into the normal adult rat substantia nigra is taken up rapidly into neurons and increases resting levels of dopamine and its metabolites for up to 28 days. Of particular note, DNSP-11 significantly improves apomorphine-induced rotational behavior, and increases dopamine and dopamine metabolite tissue levels in the substantia nigra in a rat model of PD. Unlike GDNF, DNSP-11 was found to block staurosporine- and gramicidin-induced cytotoxicity in nutrient-deprived dopaminergic B65 cells, and its neuroprotective effects included preventing the release of cytochrome c from mitochondria. Collectively, these data support that DNSP-11 exhibits potent neurotrophic actions analogous to GDNF, making it a viable candidate for a PD therapeutic. However, it likely signals through pathways that do not directly involve the GFRalpha1 receptor.PLoS ONE 01/2010; 5(3):e9752. · 4.09 Impact Factor -
Article: Olfactory ensheathing cells conditioned medium prevented apoptosis induced by 6-OHDA in PC12 cells through modulation of intrinsic apoptotic pathways.
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ABSTRACT: Olfactory ensheathing cells (OECs) express a high level of growth factors which play a very important role as neuronal support. Recent evidence in literatures showed that transplantation of OECs may improve functional restoration in 6-OHDA-induced rat model of Parkinson's disease (PD). However, the biological function of various factors released from OECs in Parkinson' disease is still unclear. In this study, we examined the effects of newborn rat OECs conditioned medium (CM) on PC12 cells. Cells treated with 6-OHDA underwent cytotoxicity and apoptotic death determined by MTT assay and Hoechst 33342/PI staining. OECs CM was able to reduce the cellular damage in PC12 cells. Further investigation results showed that CM inhibited the disruption of mitochondrial transmembrane potential, up-regulation of Bcl-2 and down-regulation of Bax. Taken together, this study indicates that CM has a neuroprotective effect on 6-OHDA induced apoptosis of PC12 cells, which is through up-regulation of the Bcl-2/Bax ratio and protection for mitochondrion.International Journal of Developmental Neuroscience 26(3-4):323-9. · 2.42 Impact Factor
