Altered glial cell line-derived neurotrophic factor (GDNF) concentrations in the brain of patients with depressive disorder: A comparative post-mortem study

2008 ◽  
Vol 23 (6) ◽  
pp. 413-420 ◽  
Author(s):  
Tanja M. Michel ◽  
Sophia Frangou ◽  
Sibylle Camara ◽  
Dorothea Thiemeyer ◽  
Julia Jecel ◽  
...  
Keyword(s):  
Depressive Disorder ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Transforming Growth Factor ◽  
Brain Area ◽  
Sandwich Elisa ◽  
Brain Regions ◽  
Control Group ◽  
Post Mortem

AbstractIntroductionA growing body of evidence suggests that the glial cell line-derived neurotrophic factor (GDNF) is involved in the aetiopathology of mood disorders. GDNF is a neurotrophic factor from the transforming growth factor-β-family, playing a role in cell development and function in the limbic system. This is the first study to examine GDNF concentration in different brain regions of patients with depressive disorder (DD).Material and MethodsWe used sandwich-ELISA-technique to ascertain GDNF concentration and Lowry assay for overall protein levels in post-mortem brain tissue of 7 patients with recurrent depressive disorder and 14 individuals without any neurological or psychiatric diagnoses. We included cortical regions as well as limbic area's (hippocampus, entorhinal cortex) basal ganglia (putamen, caudate nucleus), thalamus and cingulated gyrus.ResultsWe found a significant increase in GDNF concentration in the parietal cortex of patients with DD compared to the control group. In other regions the trend of an increased GDNF concentration did not reach statistical difference.DiscussionThis proof of concept study supports previous findings of an alteration of the GDNF in patients with depressive disorder. However, for the first time a significant increase of GDNF in a cortical brain area was found in DD.

230 EFFECT OF DIFFERENT CONCENTRATIONS OF GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTOR ON EXPRESSION OF SELF-RENEWAL RELATED GENES IN GOAT (CAPRA HIRCUS) SPERMATOGONIAL STEM CELLS

2016 ◽  
Vol 28 (2) ◽  
pp. 246
Author(s):  
A. Sharma ◽  
S. M. Shah ◽  
N. Saini ◽  
M. K. Singh ◽  
S. K. Singla ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Transforming Growth Factor ◽  
Spermatogonial Stem Cells ◽  
Capra Hircus ◽  
Control Group ◽  
Self Renewal ◽  
Percoll Density Gradient Centrifugation

Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-β superfamily produced by Sertoli cells, is essential for the self-renewal of spermatogonial stem cells in vivo. The present study evaluated the effects of different concentrations of GDNF (human recombinant expressed in Escherichia coli) on expression of some self-renewal related genes in spermatogonial stem cells (SSC). The SSC were isolated from prepubertal goat testes (3–6 months of age) by using double enzymatic digestion method and filtration through 80- and 60-µm nylon mesh filters. Further enrichment was achieved by differential plating on Datura stramonium agglutinin (DSA) lectin-coated dishes and Percoll density gradient centrifugation. The enriched cells were cultured on goat Sertoli cell feeder layer in DMEM + 10% fetal bovine serum at 37°C in a 5% CO2 incubator. Primary SSC colonies were formed within 7 to 10 days. These colonies were characterised through alkaline phosphatase and immunofluorescence staining on Day 10 for different SSC-specific protein markers. Colonies were found to be positive for DBA, THY1, PLZF, UCHL1, OCT-4, SOX2, and NANOG, and negative for c-Kit expression. These colonies were cultured for 15 days without or with supplementation of GDNF forming following groups: (1) without GDNF (control), (2) 10 ng mL–1 GDNF, (3) 20 ng mL–1 GDNF, and (4) 40 ng mL–1 GDNF. RNA was isolated from 100 colonies from 3 different trials on Day 15 of culture, and relative expression of different self-renewal related genes was determined by qRT-PCR. Relative mRNA abundance of PLZF was higher (P < 0.05) following supplementation with 40 ng mL–1 GDNF than in other groups (i.e. control, 10 and 20 ng mL–1 GDNF). Expression of BCL6B and ID4 was found to be significantly higher (P < 0.05) after supplementation of GDNF at all concentrations compared with the control group. Expression of UCHL1 was higher with addition of 20 and 40 ng mL–1 GDNF (P < 0.05), whereas expression of THY1 was higher with supplementation of 10 ng mL–1 GDNF (P < 0.05). In conclusion, GDNF was found to benefit expression of goat SSC candidate genes at a concentration of 40 ng mL–1.

scholarly journals Evaluation of Serum Glial Cell Line-derived Neurotrophic Factor in Bangladeshi Major Depressive Disorder Patients

Cureus ◽  
2019 ◽  
Author(s):  
Rajesh Das ◽  
Md Prova Zaman Emon ◽  
Sayeeda Fahmee Chowdhury ◽  
Sumaiya Huque ◽  
Tanzan Zahan ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Major Depressive

scholarly journals The major determinant of the heparin binding of glial cell-line-derived neurotrophic factor is near the N-terminus and is dispensable for receptor binding

2007 ◽  
Vol 404 (1) ◽  
pp. 131-140 ◽  
Author(s):  
Ivan Alfano ◽  
Parvez Vora ◽  
Rosemary S. Mummery ◽  
Barbara Mulloy ◽  
Christopher C. Rider
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Transforming Growth Factor ◽  
Basic Amino Acid ◽  
Transforming Growth Factor Β ◽  
Heparin Binding ◽  
Binding Sequence

GDNF (glial cell-line-derived neurotrophic factor), and the closely related cytokines artemin and neurturin, bind strongly to heparin. Deletion of a basic amino-acid-rich sequence of 16 residues N-terminal to the first cysteine of the transforming growth factor β domain of GDNF results in a marked reduction in heparin binding, whereas removal of a neighbouring sequence, and replacement of pairs of other basic residues with alanine had no effect. The heparin-binding sequence is quite distinct from the binding site for the high affinity GDNF polypeptide receptor, GFRα1 (GDNF family receptor α1), and heparin-bound GDNF is able to bind GFRα1 simultaneously. The heparin-binding sequence of GDNF is dispensable both for GFRα1 binding, and for activity for in vitro neurite outgrowth assay. Surprisingly, the observed inhibition of GDNF bioactivity with the wild-type protein in this assay was still found with the deletion mutant lacking the heparin-binding sequence. Heparin neither inhibits nor potentiates GDNF–GFRα1 interaction, and the extracellular domain of GFRα1 does not bind to heparin itself, precluding heparin cross-bridging of cytokine and receptor polypeptides. The role of heparin and heparan sulfate in GDNF signalling remains unclear, but the present study indicates that it does not occur in the first step of the pathway, namely GDNF–GFRα1 engagement.

Plasma glial cell line-derived neurotrophic factor in patients with major depressive disorder: a preliminary study

2015 ◽  
Vol 28 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Bun-Hee Lee ◽  
Jin-Pyo Hong ◽  
Jung-A Hwang ◽  
Kyoung-Sae Na ◽  
Won-Joong Kim ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Recurrent Episode ◽  
First Episode ◽  
Healthy Controls ◽  
Major Depressive ◽  
Before And After

BackgroundSome clinical studies have reported reduced peripheral glial cell line-derived neurotrophic factor (GDNF) level in elderly patients with major depressive disorder (MDD). We verified whether a reduction in plasma GDNF level was associated with MDD.MethodPlasma GDNF level was measured in 23 healthy control subjects and 23 MDD patients before and after 6 weeks of treatment.ResultsPlasma GDNF level in MDD patients at baseline did not differ from that in healthy controls. Plasma GDNF in MDD patients did not differ significantly from baseline to the end of treatment. GDNF level was significantly lower in recurrent-episode MDD patients than in first-episode patients before and after treatment.ConclusionsOur findings revealed significantly lower plasma GDNF level in recurrent-episode MDD patients, although plasma GDNF levels in MDD patients and healthy controls did not differ significantly. The discrepancy between our study and previous studies might arise from differences in the recurrence of depression or the ages of the MDD patients.

scholarly journals Glial cell line–derived neurotrophic factor–supplemented hibernation of fetal ventral mesencephalic neurons for transplantation in Parkinson disease: long-term storage

2002 ◽  
Vol 13 (5) ◽  
pp. 1-6 ◽  
Author(s):  
Adam O. Hebb ◽  
Kari Hebb ◽  
Arun C. Ramachandran ◽  
Ivar Mendez
Keyword(s):  
Parkinson Disease ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Fetal Tissue ◽  
Cresyl Violet ◽  
Control Group ◽  
Long Term Storage ◽  
Cell Counts ◽  
Fresh Culture

Object Investigation of fetal dopaminergic tissue transplantation is being conducted in animal models and clinical trials as a potential treatment for advanced Parkinson disease (PD). Because the availability of fetal tissue is limited, however, the duration of its storage prior to transplantation is a key practical issue. Longer storage times may enable fetal tissue obtained over several days to be pooled together for transplantation in a recipient. Glial cell line–derived neurotrophic factor (GDNF) has been shown to improve survival of stored human dopaminergic tissue prior to transplantation. The objective of this study was to evaluate GDNF-supplemented hibernation of fetal dopaminergic tissue for extended periods of 6 to 15 days. Methods A total of 27 rat ventral mesencephalons (VMs) were obtained in gestation Day 14 rat fetuses, and three were cultured immediately (fresh-culture control group). The remaining 24 VMs were divided sagittally along the mid-line to form 48 equal pieces of hemimesencephalons. Twenty-four pieces were stored with GDNF-supplemented hibernation medium for 6, 9, 12, or 15 days, and the 24 “partner” hemimesencephalons were stored in control hibernation medium for the same periods of time. Tissue was cultured for 48 hours and processed for tyrosine hydroxylase (TH) immunoreactivity and cresyl violet. Cell counts for all cultures and percentage of TH-immunoreactive cells were obtained. The percentage of TH-positive cells for the fresh control group was 6.3 ± 0.5%; that measured in cultures derived from tissue hibernated in GDNF-supplemented medium was significantly increased at 6 and 9 days posthiber-nation compared with the fresh-culture control group and the partner groups stored in hibernation medium only. No significant increase in percentage of TH-immunoreactive cells was observed in the 12- and 15-day hibernation groups. Conclusions In summary the authors found that fetal dopaminergic tissue can safely be stored up to 9 days in GDNF-supplemented hibernation medium. Furthermore the percentage of TH-immunoreactive cells is significantly increased after 6 and 9 days of storage in this medium, improving the yield of TH-positive cells prior to transplantation. These observations may have important clinical implications for collecting fetal dopaminergic cells and improving their survival after transplantation.

Glial cell line—derived neurotrophic factor—supplemented hibernation of fetal ventral mesencephalic neurons for transplantation in Parkinson disease: long-term storage

2003 ◽  
Vol 98 (5) ◽  
pp. 1078-1083 ◽  
Author(s):  
Adam O. Hebb ◽  
Kari Hebb ◽  
Arun C. Ramachandran ◽  
Ivar Mendez
Keyword(s):  
Parkinson Disease ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Storage Time ◽  
Fetal Tissue ◽  
Control Group ◽  
Content Type ◽  
Cell Counts ◽  
Fine Print

Object. Transplantation of fetal dopaminergic tissue is being investigated in animal models and clinical trials for its potential as a treatment for advanced Parkinson disease. At the same time, the availability of fetal tissue is limited, making its storage time prior to transplantation a key practical issue. Although it results in a smaller percentage of surviving cells, a longer storage time enables fetal tissue obtained over several days to be pooled for transplantation in a recipient. Glial cell line—derived neurotrophic factor (GDNF) has been shown to improve survival of human dopaminergic tissue that has been stored prior to transplantation. The objective of this study was to evaluate the effects on fetal dopaminergic tissue of GDNF-supplemented hibernation for extended periods of 6 to 15 days. Methods. The ventral mesencephalon (VM) was harvested in a total of 27 14-day-old rat fetuses, and three VMs were cultured immediately (fresh control group). The remaining 24 VMs were divided sagittally along the midline to yield 48 equal pieces of hemimesencephalon. Twenty-four pieces were stored with GDNF-supplemented hibernation medium for 6, 9, 12, or 15 days, and the 24 “partner” hemimesencephalon pieces were stored in control hibernation medium for the same periods of time. Tissue was cultured for 48 hours and processed for tyrosine hydroxylase (TH) immunoreactivity and double-stained with cresyl violet. Cell counts for all cultures and the percentage of TH-immunoreactive cells were obtained. The percentage of TH-immunoreactive cells for the fresh control group was 6.3 ± 0.5%. The percentage of TH-immunoreactive cells in cultures derived from tissue stored in GDNF-supplemented medium was significantly increased at 6 and 9 days posthibernation compared with the fresh control group and the “partner” groups stored in hibernation medium only. No significant increase in the percentage of TH-immunoreactive cells was observed in the 12- and 15-day groups. Conclusions. In this study the authors have demonstrated that fetal dopaminergic tissue can be safely stored for up to 9 days in GDNF-supplemented hibernation medium. Furthermore, the percentage of TH-immunoreactive cells is significantly increased after 6 and 9 days of storage in this medium, improving the yield of TH-immunoreactive cells prior to transplantation. These observations have practical clinical implications for collecting fetal dopaminergic cells and improving their survival after transplantation.

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