Multiple Astrocyte Transcripts Encode Nigral Trophic Factors in Rat and Human

Schaar, Dale; Sieber, Beth-Anne; Sherwood, Ann C.; Dean, Deyrick; Mendoza, Grace; Ramakrishnan, Lakshmi; Dreyfus, Cheryl F.; Black, Ira B.

doi:10.1006/exnr.1994.1218

Cited by 45 publications

(24 citation statements)

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“…This is identical with ATF-1 cDNA, a previously reported short form of human GDNF (Schaar et al, 1994). To exclude the possibility that the truncated GDNF sequence we isolated arose from a polymorphic abnormality, we screened an additional human skeletal muscle cDNA library and found an identical truncated GDNF cDNA (data not shown).…”

Section: Discussionmentioning

confidence: 78%

Prominent expression of glial cell line-derived neurotrophic factor in human skeletal muscle

et al. 1998

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Glial cell line-derived neurotrophic factor (GDNF) has been shown to exert neurotrophic effects on motor neurons as well as mesencephalic dopaminergic neurons. Because GDNF promotes survival of motor neurons in vivo and in vitro and rescues motor neurons from naturally occurring cell death, the potential use of GDNF for treatment of motor neuron diseases has been a major focus of recent research. The expression of GDNF in humans, however, has not been fully examined. In the present study, we examined the expression of GDNF in adult human muscle by Northern blot, reverse transcriptase polymerase chain reaction (RT-PCR), and immunohistochemical analyses to address physiological roles of GDNF in humans. Northern blot analysis demonstrated high expression of GDNF mRNA in human skeletal muscle when compared to that of mouse. Intense GDNF immunoreactivity was observed in the vicinity of plasma membranes of skeletal muscle, particularly at neuromuscular junctions. GDNF immunoreactivity was also observed within the axons and surrounding Schwann cells of peripheral nerves. However, RT-PCR detected expression of GDNF mRNA only in skeletal muscle, and not within the anterior horn cells of human spinal cord. These results suggest that GDNF is produced by skeletal muscle and taken up at the nerve terminals for retrograde transport by axons. Thus, GDNF in human skeletal muscle may be involved in promoting motor neuron survival as a target-derived neurotrophic factor.

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Section: Discussionmentioning

confidence: 78%

Prominent expression of glial cell line-derived neurotrophic factor in human skeletal muscle

et al. 1998

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“…34 The presence of GDNF messenger RNA (mRNA) in the astrocytes of substantia nigra, 35,36 and the high sensitivity of DA neurons to this neurotrophin make GDNF a likely candidate for the yet unidentified VPA-induced, astrocytes-secreted neurotrophic substance. [37][38][39] To test this possibility, we used real-time PCR to quantify GDNF mRNA.…”

Section: Resultsmentioning

confidence: 99%

Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes

et al. 2006

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Valproate (VPA), one of the mood stabilizers and antiepileptic drugs, was recently found to inhibit histone deacetylases (HDAC). Increasing reports demonstrate that VPA has neurotrophic effects in diverse cell types including midbrain dopaminergic (DA) neurons. However, the origin and nature of the mediator of the neurotrophic effects are unclear. We have previously demonstrated that VPA prolongs the survival of midbrain DA neurons in lipopolysaccharide (LPS)-treated neuron-glia cultures through the inhibition of the release of pro-inflammatory factors from microglia. In this study, we report that VPA upregulates the expression of neurotrophic factors, including glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) from astrocytes and these effects may play a major role in mediating VPA-induced neurotrophic effects on DA neurons. Moreover, VPA pretreatment protects midbrain DA neurons from LPS or 1-methyl-4-phenylpyridinium (MPP þ )-induced neurotoxicity. Our study identifies astrocyte as a novel target for VPA to induce neurotrophic and neuroprotective actions in rat midbrain and shows a potential new role of cellular interactions between DA neurons and astrocytes. The neurotrophic and neuroprotective effects of VPA also suggest a utility of this drug for treating neurodegenerative disorders including Parkinson's disease. Moreover, the neurotrophic effects of VPA may contribute to the therapeutic action of this drug in treating bipolar mood disorder that involves a loss of neurons and glia in discrete brain areas.

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“…Within the nervous system, GDNF mRNA transcripts have been localized to glial cells (Springer et al, 1995;Ho et al, 1995;Schaar et al, 1994), macrophages (Liberatore et al, 1997) and to select neuronal populations (Humpel et al, 1994;Schmidt-Kastner et al, 1994;Pochon et al, 1997;Bar et al, 1998). In vitro studies have demonstrated GDNF to promote the survival and/or differentiation of numerous neuronal populations (Lin et al, 1993;Zurn et al, 1994;Trupp et al, 1995;Buj-Bello et al, 1995;Mount et al, 1995;Molliver et al, 1997).…”

Section: Introductionmentioning

confidence: 94%

“…In its natural state, GDNF exists as a glycosylated homodimer of approximately 39 kDa, each monomer containing seven conserved cysteine residues, forming intra-and interdisulfide bonds characteristic of transforming growth factor ␤ (TGF␤) superfamily members. Originally synthesized as a prepropeptide, proteolytic cleavage of a consensus signal sequence and prepro region yields the mature 134-amino acid form (Lin et al, 1993;Schaar et al, 1994). GDNF is transcribed from a single gene, located on human chromosome 5 at p12-p13.1 (Schindelhauer et al, 1995), and through alternative splicing, generates at least two transcripts, the smaller of which contains a 26-amino acid deletion within the prepro region (Suter-Crazzolara and Unsicker, 1994;Scharr et al, 1994).…”

Section: Introductionmentioning

confidence: 96%

Differential regulation of glial cell line-derived neurotrophic factor (GDNF) expression in human neuroblastoma and glioblastoma cell lines

Verity¹,

Wyatt²,

Lee³

et al. 1999

J. Neurosci. Res.

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Human SK-N-AS neuroblastoma and U-87MG glioblastoma cell lines were found to secrete relatively high levels of glial cell line-derived neurotrophic factor (GDNF). In response to growth factors, cytokines, and pharmacophores, the two cell lines differentially regulated GDNF release. A 24-hr exposure to tumor necrosis factor-alpha (TNFalpha; 10 ng/ml) or interleukin-1beta (IL-1,; 10 ng/ml) induced GDNF release in U-87MG cells, but repressed GDNF release from SK-N-AS cells. Fibroblast growth factors (FGF)-1, -2, and -9 (50 ng/ml), the prostaglandins PGA2, PGE2, and PGI2 (10 microM), phorbol 12,13-didecanoate (PDD; 10 nM), okadaic acid (10 nM), dexamethasone (1 microM), and vitamin D3 (1 microm) also differentially effected GDNF release from U-87MG and SK-N-AS cells. A result shared by both cell lines, was a two- to threefold increase in GDNF release by db-cAMP (1 mM), or forskolin (10 microM). In general, analysis of steady-state GDNF mRNA levels correlated with changes in extracellular GDNF levels in U-87MG cells but remained static in SK-N-AS cells. The data suggest that human GDNF synthesis/release can be regulated by numerous factors, signaling through multiple and diverse secondary messenger systems. Furthermore, we provide evidence of differential regulation of human GDNF synthesis/release in cells of glial (U-87MG) and neuronal (SK-N-AS) origin.

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Multiple Astrocyte Transcripts Encode Nigral Trophic Factors in Rat and Human

Cited by 45 publications

References 0 publications

Prominent expression of glial cell line-derived neurotrophic factor in human skeletal muscle

Prominent expression of glial cell line-derived neurotrophic factor in human skeletal muscle

Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes

Differential regulation of glial cell line-derived neurotrophic factor (GDNF) expression in human neuroblastoma and glioblastoma cell lines

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