Specific effects of platelet derived growth factor (PDGF) on fetal rat and human dopaminergic neurons in vitro

Abstract

The neurotrophic effects of the BB isoform of platelet-derived growth factor (PDGF) on rat and human fetal mesencephalic dopaminergic neurons have been characterized in vitro. A dose-response analysis demonstrated maximal responses at 30 ng/ml of PDGF-BB. This concentration resulted in a marked increase in the survival and neurite outgrowth from rat and human tyrosine hydroxylase-(TH) positive, presumed dopaminergic neurons after 7 days in vitro. The effects of PDGF-BB on survival of TH-positive neurons were comparable to those of brain-derived neurotrophic factor (BDNF), whereas neurite outgrowth was more pronounced after addition of BDNF. The combination of BDNF and PDGF-BB yielded no additive effects. Double immunohistochemical staining of rat cultures demonstrated PDGF beta-receptors on about 90% of the TH-positive neurons. PDGF-BB treatment of rat mesencephalic cultures induced an upregulation of c-fos and TH mRNA with maximal levels after 0.5-2 h as assessed by quantitative PCR analysis. An increased number of Fos protein-positive cells was detected immunohistochemically after 4 h of PDGF-BB treatment. The present results provide further evidence for specific and direct effects of PDGF-BB on gene expression, survival and neurite outgrowth of mesencephalic dopaminergic neurons of rat and human origin.

Platelet-derived growth factor protects neurons against gp120-mediated toxicity

“…Interestingly, pre-treatment of neuronal cells with PDGF-BB abrogated neuronal retraction and resulted in reduced cell death compared with cells treated with gp120 alone. PDGF is known to mediate its neuroprotective effect through the induction of neurite outgrowth, as demonstrated in a variety of in vitro neuronal systems, including fetal rat and human dopaminergic neurons (Othberg et al, 1995), SH-SY5Y cells (Hynds et al, 1997) and hippocampal HiB5 cells (Sung et al, 2001). Other neurotrophic factors such as FGF and BDNF have earlier been documented to play a role in rescuing cells against gp120-mediated toxicity (Bachis and Mocchetti, 2005;Hashimoto et al, 2002).…”

“…Since PDGF-B chain is produced by healthy neurons (Smits et al, 1991) and has neuroprotective properties (Hynds et al, 1997;Mohapel et al, 2005;Othberg et al, 1995;Sung et al, 2001;Tseng and Dichter, 2005), we hypothesized that pre-treatment of neurons with PDGF-BB protein could protect against gp120-mediated neurotoxicity.…”

Characterization of Regenerative Phenotype of Unrestricted Somatic Stem Cells (USSC) from Human Umbilical Cord Blood (hUCB) by Functional Secretome Analysis

“…Comparison of all secreted proteins or proteins predicted to be secreted according to the literature revealed that USSC secrete at least 31 proteins that are known to be involved in neurite growth or axonal regrowth (Table I) including the neurotrophic factors mesencephalic astrocyte-derived neurotrophic factor (MANF) (37), neudesin (38), and neuron-derived neurotrophic factor (NDNF) (39) as well as the growth factors angiopoietin-2 (40), growth/differentiation factor 15 (GDF-15) (41), hepatoma-derived growth factor (HDGF) (42), PDGF (43), and transforming growth factor-beta1/-2 (TGF-␤1/TGF-␤2) (44 -45). Moreover, we identified several matrix-and membrane-associated proteins, e.g.…”

Platelet-derived Growth Factor Induces a Long-term Inhibition of -Methyl-D-aspartate Receptor Function

“…It is likely that this elevation in PDGF levels is involved not only in the pathogenesis of these conditions but also in the tissue repair processes associated with these diseases. In this regard, it has been shown that PDGF exerts neurotrophic effects on GABAergic and dopaminergic neurons (17,18) and that it protects hip-pocampal neurons against energy deprivation and oxidative injury in vitro (19).…”