OBJECTIVE: Some clinical studies have found alterations in the levels of serum brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) after applying antidepressant treatment in patients with major depressive disorder (MDD). We evaluated the serum BDNF and GDNF levels before and after 12 weeks of antidepressant treatment in MDD outpatients. METHODS: Serum BDNF and GDNF levels were measured in 23 female MDD outpatients at baseline and after 12 weeks of treatment. The severity of depression was measured with the Hamilton Depression Rating Scale-17 (HAMD-17). Remission of MDD to the treatment was defined as a posttreatment HAMD-17 score of <7. RESULTS: Among MDD patients, 19 (82.6%) subjects were in mild to moderate depression. The whole MDD patients had significantly higher serum BDNF and GDNF levels at baseline than those after 12 weeks of antidepressant treatment. The baseline serum BDNF and GDNF levels did not significantly between the remission and nonremission groups. The significant alteration in both BDNF and GDNF levels after antidepressant treatment were observed in patients with remission. CONCLUSION: The present study suggests that the baseline serum BDNF and GDNF levels are higher than the posttreatment levels in some mild-to-moderate MDD outpatients and the significant alteration in BDNF and GDNF level after treatment were observed in patients with remission.
Brain-Derived Neurotrophic Factor* ; Depression ; Depressive Disorder, Major* ; Female* ; Glial Cell Line-Derived Neurotrophic Factor* ; Humans ; Outpatients*

OBJECTIVEThis research aims to study the changes in pain threshold and glial cell line-derived neurotrophic factor (GDNF) in a Sprague Dawley (SD) rat model oftrigeminal neuralgia.

METHODSA total of 36 male SD rats were randomly divided into three groups: operative, sham-operative, and control. In the operative group, a chronic constriction injury (CCI) was caused by placing loose chromic gut ligatures around the right infraorbital nerve (ION). In the sham-operative group, the right ION was subjected to the same procedure, but without ligation. In the control group, the right ION was not subjected to any treatment. The pain thresholds of the three groups were recorded at different times after the operation. The GDNF expression in each group was analyzed via immunohistochemical staining.

RESULTSAn allodynia to mechanical stimulation in the region of the ligated ION was observed starting on the 2nd week after operation. Pain thresholds started to increase gradually from the 6th week and returned to the original level at the 10th to 12th week after operation. Cells that expressed the GDNF markedly increased in number in the operative group with changes observed at different times.

CONCLUSIONWe use chronic constriction injury to the infraorbital nerve (CCI-ION) to establish a trigeminal neuralgia-like animal model in SD rats. GDNF may play a role in regulating pain by promoting the restoration and regeneration of nerve fibers.

Animals ; Constriction ; Disease Models, Animal ; Glial Cell Line-Derived Neurotrophic Factor ; Glial Cell Line-Derived Neurotrophic Factors ; Hyperalgesia ; Male ; Pain Threshold ; Rats ; Rats, Sprague-Dawley ; Trigeminal Neuralgia

BACKGROUND/AIMS: Dependent receptor can transmit both positive signal: proliferation, differentiation or migration; and negative signal: apoptosis. It depends on the presence of its ligand. This study was performed to determine the effects of transfection of dependent receptors in human colon cancer cell lines. METHODS: Two dependent receptors (rearranged during transfection [RET]9 and RET51) were transfected into three human colon cancer cell lines: SW48, RKO and V400. Then, half of them were treated with glial cell line-derived neurotrophic factor (GDNF). Using ELISA and caspase assay, apoptosis was measured. Dose-response relation between GDNF and apoptosis was also analyzed. A pcDNA was used as an empty vector. RESULTS: After transfection of RET51, apoptosis was increased in SW48 (70% with ELISA and 119% with caspase assay) and RKO (255% with ELISA and 106% with caspase assay) cell lines when compared with the pcDNA group. V400 cell line did not show increased apoptosis. Transfection of RET9 did not induce apoptosis in all of the three human colon cancer cell lines. Treatment with GDNF 12 hours after transfection of RET51 decreased apoptosis in SW48 (66% with ELISA and 60% with caspase assay) and RKO (39% with ELISA and 57% with caspase assay) when compared with the cell lines transfected with RET51 only. Apoptosis was down-regulated with increasing concentration of GDNF in RKO cell line. CONCLUSIONS: This study showed that the apoptosis of human colon cancer cell line can be controlled by manipulating the dependent receptors and its ligands. We present the possibility of therapeutic method using dependent receptor in colon cancer.
Apoptosis ; Cell Line ; Colon ; Colonic Neoplasms ; Enzyme-Linked Immunosorbent Assay ; Glial Cell Line-Derived Neurotrophic Factor ; Humans ; Ligands ; Transfection

OBJECTIVETo investigate telomerase activity in rabbit bone marrow stromal cells (BMSCs) during their committed differentiation in vitro along neural pathway and the effect of glial cell line-derived neurotrophic factor (GDNF) on the expression of telomerase.

METHODSBMSCs were acquired from rabbit marrow and divided into control group, GDNF (10 ng/ml) group. Cytokine.NSCs medium (prepared by our lab, Patent No. ZL02134314. 4) supplemented with 10 percent fetal bovine serum (FBS) was used to induce BMSCs differentiation along neural pathway. Fluorescent immunocytochemistry was employed to identify the expressions of Nestin, neuron-specific endase (NSE), and gial fibrillary acidic protein (GFAP). The growth curves of the cells and the status of cell cycles were analyzed, respectively. During the differentiation, telomerase activities were detected using the telomeric repeat amplification protocol-enzyme-linked immunosorbent assay (TRAP-ELISA).

RESULTSBMSCs were successfully induced to differentiate along neural pathway and expressed specific markers of fetal neural epithelium, mature neuron and glial cells. Telomerase activities were undetectable in BMSCs during differentiation along neural pathway. Similar changes of cell growth curves, cell cycle status and telomerase expression were observed in the two groups.

CONCLUSIONSRabbit BMSCs do not display telomerase activity during differentiation along neural pathway. GDNF shows little impact on proliferation and telomerase activity of BMSCs.

Animals ; Bone Marrow Cells ; enzymology ; Cell Differentiation ; Glial Cell Line-Derived Neurotrophic Factor ; Immunohistochemistry ; Rabbits ; Stromal Cells ; enzymology ; Telomerase ; metabolism

OBJECTIVETo study on the analgesic mechanism of electroacupuncture (EA) in the rat of adjuvant arthritis (AA).

METHODSForty-eight SD rats were randomly divided into a blank control group (n = 8), an inflammatory group (n = 10), an acupoint EA group (n = 10), a non-acupoint EA group (n = 10) and a contralateral acupoint EA group (n = 10). Complete Freund's adjuvant (CFA) 50 microL were injected into the left malleolus' articular cavity in the rats except the blank control group for preparing single local adjuvant arthritis (AA) model. EA was given every other day to the acupoint EA group, the non-acupoint EA group and the contralateral acupoint EA group. The improving effects of EA at "Huantiao" (GB 30) and "Yanglingquan" (GB 34) on the dorsal flexion pain score and the swell of dorsum of hind paw were investigated, and effects of EA on Glial cell line-derived neurotrophic factor (GDNF) positive cells immunoreactivity in the inflammatory tissue of the AA rats on the 14th day after injection of adjuvant were observed with immunohistochemical technique.

RESULTSHyperalgesia and local swell, and GDNF in the dermal and subcutaneous tissue around the inflammatory ankle joint in the inflammatory groups were significantly higher than those in the blank control group. EA on the ipsilateral and contralateral acupoints reduced the pain, promoted the recovery of swell, and decreased the positive area percentage and mean optical density of GDNF positive cells in the dermal and the subcutaneous tissues. However, the non-acupoint EA group did not have this action.

CONCLUSIONEA can regulate expression of GDNF in local dermal tissue of the inflammatory focus in the AA rat, so as to exert the anti-inflammatory and analgesic effects.

Animals ; Arthritis, Experimental ; metabolism ; therapy ; Electroacupuncture ; Glial Cell Line-Derived Neurotrophic Factor ; analysis ; Immunohistochemistry ; Rats ; Rats, Sprague-Dawley

PURPOSE: Medullary sponge kidney (MSK) is a rare congenital disease characterized by diffuse ectasia or dilatation of precalyceal collecting tubules. MSK incidence and prevalence in the general population is uncertain and only a few patients are reported especially in the pediatric age. There has been increasing reports of patients with MSK who have other malformative disorders. Also several case reports concerning about etiological association of some genes. METHODS: Collaborative study through nation-wide survey was done to investigate the incidence and etiological association of some genes such as GDNF gene, ATP6V1B1, ATP6V0A4 gene in developing MSK in Korean children. RESULTS: Four cases of MSK who have various other malformative disorders were collected. There are no mutations of GDNF gene, ATP6V1B1, ATP6V0A4 gene in all patients. CONCLUSION: MSK is one of the very rare diseases in pediatric age. The etiological association of GDNF gene , ATP6V1B1, ATP6V0A4 gene in developing MSK in Korean children is not proved.
Child ; Dilatation ; Dilatation, Pathologic ; Glial Cell Line-Derived Neurotrophic Factor ; Humans ; Incidence ; Medullary Sponge Kidney ; Prevalence ; Rare Diseases

Glial cell line-derived neurotrophic factor (GDNF) has been reported to be involved in negatively regulating the effects of addictive disorders. The objective of this study was to investigate alterations in the levels of GDNF in patients with Internet gaming disorder (IGD) and to assess the relationship between GDNF levels and the severity of IGD indices. Nineteen male patients with IGD and 19 sexmatched control subjects were evaluated for alteration of plasma GDNF levels and for relationship between GDNF levels and clinical characteristics of Internet gaming, including the Young's Internet Addiction Test (Y-IAT). The GDNF levels were found to be significantly low in patients with IGD (103.2±62.0 pg/mL) compared with the levels of controls (245.2±101.6 pg/mL, p<0.001). GDNF levels were negatively correlated with Y-IAT scores (Spearman's rho=-0.645, p=<0.001) and this negative correlation remained even after controlling for multiple variables (r=-0.370, p=0.048). These findings support the assumed role of GDNF in the regulation of IGD.
Case-Control Studies ; Glial Cell Line-Derived Neurotrophic Factor ; Humans ; Immunoglobulin D ; Internet ; Male ; Neuroglia ; Pilot Projects ; Plasma

OBJECTIVE: Cellular diversity in the mammalian central nervous system is originated from precursor cells present in the neural ectoderm. The multipotent neural stem cells(NSCs) rapidly proliferate to give rise to transiently dividing progenitors that eventually differentiate into several cell types of neural cells. The authors investigate whether NSCs could differentiate neurons and glia and express neurotrophic factor. METHODS: To establish human neural cell lines, we isolated neural stem cells from human fetal telencephalon. Secondly, to investigate the expression of neurotrophic factor, basic fibroblast growth factor(bFGF), brain-derived neurotrophic factor(BDNF) and glial derived neurotrophic factor(GDNF) in rat and human cell, mRNA expressions of bFGF, BDNF and GDNF were detected by the reverse transcripted polymerase chain reaction(RT-PCR) analysis. RESULTS: In the NSCs cultures of embryonic rat striata and human fetal telencephalon, we demonstrated that bFGF induces the proliferation of stem cell, which give rise to spheres of undifferentiated cell that generate neurons and glia. Also, neurotrophic factor transcripts were identified using PCR in rat and human NSCs. CONCLUSION: These results demonstrate that human NSCs derived from human fetal telencephalon could differentiate neurons and glia and express neurotrophic factors. Therefore, NSCs may be an important key for the therapeutic application of neurotrophic factors.
Animals ; Brain-Derived Neurotrophic Factor ; Cell Line ; Central Nervous System ; Ectoderm ; Fibroblasts ; Glial Cell Line-Derived Neurotrophic Factor ; Humans* ; Nerve Growth Factors* ; Neural Stem Cells* ; Neuroglia ; Neurons ; Polymerase Chain Reaction ; Rats ; RNA, Messenger* ; Stem Cells ; Telencephalon*

BACKGROUNDSpinal cord injury (SCI) is a serious neurological injury that often leads to permanent disabilities for the victims. The aim of this study was to determine the effects of glial-derived neurotrophic factor (GDNF) mediated by recombinant adeno-associated virus type 2 (rAAV2) alone or in combination with early rehabilitation training on SCI.

METHODSSCI was induced on the T8-9 segments of the spinal cord by laminectomy in adult male Sprague-Dawley rats. Then besides the sham operation group, the SCI rats were randomly divided into four groups: natural healing group, gene therapy group, rehabilitation training group, and combination therapy group (gene therapy in combination with rehabilitation training). Motor dysfunction, protein expression of GDNF, edema formation, and cell injury were examined 7, 14, and 21 days after trauma.

RESULTSThe topical application of rAAV-GDNF-GFP resulted in strong expression of GDNF, especially after the 14th day, and could protect the motor neuron cells. Early rehabilitative treatment resulted in significantly improved motor function, reduced edema formation, and protected the cells from injury, especially after the 7th and 14th days, and increased the GDNF expression in the damaged area, which was most evident after Day 14. The combined application of GDNF and early rehabilitative treatment after SCI resulted in a significant reduction in spinal cord pathology and motor dysfunction after the 7th and 14th days.

CONCLUSIONThese observations suggest that rAAV2 gene therapy in combination with rehabilitation therapy has potential clinical value for the treatment of SCI.

Animals ; Cell Line ; Dependovirus ; genetics ; Glial Cell Line-Derived Neurotrophic Factor ; genetics ; physiology ; Humans ; Immunohistochemistry ; Male ; Motor Activity ; genetics ; physiology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; metabolism

BACKGROUND: For peripheral nerve regeneration, recent attentions have been paid to the nerve conduits made by tissue-engineering technique. Three major elements of tissue-engineering are cells, molecules, and scaffolds. METHODS: In this study, the attachments of nerve cells, including Schwann cells, on the nerve conduit and the effects of both growth factor and adhesion molecule on these attachments were investigated. RESULTS: The attachment of rapidly-proliferating cells, C6 cells and HS683 cells, on nerve conduit was better than that of slowly-proliferating cells, PC12 cells and Schwann cells, however, the treatment of nerve growth factor improved the attachment of slowly-proliferating cells. In addition, the attachment of Schwann cells on nerve conduit coated with fibronectin was as good as that of Schwann cells treated with glial cell line-derived neurotrophic factor (GDNF). CONCLUSIONS: Growth factor changes nerve cell morphology and affects cell cycle time. And nerve growth factor or fibronectin treatment is indispensable for Schwann cell to be used for implantation in artificial nerve conduits.
Animals ; Attention ; Cell Cycle ; Fibronectins ; Glial Cell Line-Derived Neurotrophic Factor ; Nerve Growth Factor ; Neurons* ; PC12 Cells ; Peripheral Nerves* ; Regeneration* ; Schwann Cells ; Tenascin