Granulocyte colony-stimulating factor is not protective against selective dopaminergic cell death in vitro

Henze, Carmen; Lescot, Thomas; Traver, Sabine; Salthun-Lassalle, Bénédicte; Hirsch, Étienne C.; Michel, Patrick P.; Hartmann, Andréas

doi:10.1016/j.neulet.2005.03.041

Cited by 6 publications

(6 citation statements)

References 15 publications

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“…In contrast to our results, a very recent study failed to detect protective effects of G‐CSF in dopaminergic neurons in primary neuronal midbrain cultures (Henze et al . 2005).…”

Section: Discussioncontrasting

confidence: 99%

Granulocyte‐colony stimulating factor is neuroprotective in a model of Parkinson's disease

Meuer¹,

Pitzer²,

Teismann³

et al. 2006

Journal of Neurochemistry

109

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We have recently shown that the hematopoietic GranulocyteColony Stimulating Factor (G-CSF) is neuroprotective in rodent stroke models, and that this action appears to be mediated via a neuronal G-CSF receptor. Here, we report that the G-CSF receptor is expressed in rodent dopaminergic substantia nigra neurons, suggesting that G-CSF might be neuroprotective for dopaminergic neurons and a candidate molecule for the treatment of Parkinson's disease. Thus, we investigated protective effects of G-CSF in 1-methyl-4-phenylpyridinium (MPP + )-challenged PC12 cells and primary neuronal midbrain cultures, as well as in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. Substantial protection was found against MPP + -induced dopaminergic cell death in vitro. Moreover, subcutaneous application of G-CSF at a dose of 40 lg/Kg body weight daily over 13 days rescued dopaminergic substantia nigra neurons from MPTP-induced death in aged mice, as shown by quantification of tyrosine hydroxylase-positive substantia nigra cells. Using HPLC, a corresponding reduction in striatal dopamine depletion after MPTP application was observed in G-CSF-treated mice. Thus our data suggest that G-CSF is a novel therapeutic opportunity for the treatment of Parkinson's disease, because it is well-tolerated and already approved for the treatment of neutropenic conditions in humans.

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“…In contrast to our results, a very recent study failed to detect protective effects of G‐CSF in dopaminergic neurons in primary neuronal midbrain cultures (Henze et al . 2005).…”

Section: Discussioncontrasting

confidence: 99%

Granulocyte‐colony stimulating factor is neuroprotective in a model of Parkinson's disease

Meuer¹,

Pitzer²,

Teismann³

et al. 2006

Journal of Neurochemistry

109

View full text Add to dashboard Cite

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“…G-CSF also prevented dopaminergic neurons against 6-OHDAinduced degeneration [56]. In contrast, Henze et al did not observe that G-CSF prevented MPTP-induced dopaminergic neuron death in primary neuronal midbrain cultures [100].This apparent discrepancy could be due to the lower G-CSF concentrations (0.1-10 ng/ml) used in Henze's study compared with Meuer's work (30-50 ng/ml). In animals with spinal cord compression lesion, treatment with G-CSF (from day 7 to 11 post-injury) had higher the Basso-Beattie-Bresnehan scores and better recovery of hind limb sensitivity than controls injected with saline [101].…”

Section: Evidence For Neuroprotection Of G-csfmentioning

confidence: 79%

“…G‐CSF also prevented dopaminergic neurons against 6‐OHDAinduced degeneration [56]. In contrast, Henze et al did not observe that G‐CSF prevented MPTP‐induced dopaminergic neuron death in primary neuronal midbrain cultures [100]. This apparent discrepancy could be due to the lower G‐CSF concentrations (0.1–10 ng/ml) used in Henze's study compared with Meuer's work (30–50 ng/ml).…”

Section: The Neuroprotection Of G‐csf In Cerebral Ischemia and Neurodmentioning

confidence: 99%

Cell biology and clinical promise of G‐CSF: immunomodulation and neuroprotection

Xiao

Lü

Link

2007

J Cellular Molecular Medi

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In the light of the enthusiasm to use of recombinant human granulocyte colony-stimulating factor (G-CSF) for immunomodulation and neuroprotection, it should be remembered that the current knowledge is based on a century of laborious research. G-CSF is a pleiotropic cytokine playing a major role as regulator of haematopoiesis. Although the precise mechanisms of G-CSF are not known, there is growing evidence supporting the notion that G-CSF also exerts profound immunoregulatory effect in adaptive immunity and has a neuroprotective role in both cerebral ischemia and neurodegeneration. Here, we describe the immunomodulation and the neuroprotection that can be achieved with G-CSF, and summarize possible mechanisms of G-CSF as a potential therapeutic agent in autoimmune diseases and neurological disorders. Our understanding of these novel sites of action of G-CSF has opened therapeutic avenues for the treatment of autoimmune diseases and neurological disorders, and has translated the beneficial effects of G-CSF from basic experiments to clinical patients.

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“…Treatment of rat embryonic primary mesencephalic cell cultures with G‐CSF was recently reported to fail to promote the survival of dopamine (DA) neurons, based on the significant increase in the number of microglial cells observed after G‐CSF treatment (Henze et al . 2005).…”

Section: Discussionmentioning

confidence: 99%

Recombinant human granulocyte colony‐stimulating factor protects against MPTP‐induced dopaminergic cell death in mice by altering Bcl‐2/Bax expression levels

Cao¹,

Arai²,

Ren³

et al. 2006

Journal of Neurochemistry

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Granulocyte colony-stimulating factor (G-CSF) has been used for the treatment of neutropenia in hematologic disorders. The neuroprotective effects of G-CSF were reported in neurological disease models. In the present study, we examined whether G-CSF can protect dopaminergic neurons against MPTP-induced cell death in a mouse model of Parkinson's disease. Mice of one group were injected intraperitoneally with MPTP for five consecutive days, those of another group with MPTP and intraperitoneal G-CSF at 2 days and 1 day before the first MPTP injection, and 30 min before each MPTP injection, while control mice received saline injections. Immunohistochemistry, western blotting analysis, and HPLC were performed to evaluate damage of substantia nigra dopaminergic neurons and expression of Bcl-2 and Bax protein. MPTP induced dopaminergic cell death in the substantia nigra. G-CSF significantly prevented MPTP-induced loss of tyrosine hydroxylasepositive neurons (p < 0.05), increased Bcl-2 protein and decreased Bax protein expression. Our findings indicate that G-CSF provides neuroprotection against MPTP-induced cell death and this effect is mediated by increasing Bcl-2 expression levels and decreasing Bax expression levels in C57BL/6 mice.

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Granulocyte colony-stimulating factor is not protective against selective dopaminergic cell death in vitro

Cited by 6 publications

References 15 publications

Granulocyte‐colony stimulating factor is neuroprotective in a model of Parkinson's disease

Granulocyte‐colony stimulating factor is neuroprotective in a model of Parkinson's disease

Cell biology and clinical promise of G‐CSF: immunomodulation and neuroprotection

Recombinant human granulocyte colony‐stimulating factor protects against MPTP‐induced dopaminergic cell death in mice by altering Bcl‐2/Bax expression levels

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