• Advances in pediatric surgery
• /
• v.7 no.1
• /
• pp.15-20
• /
• 2001

The pathophysiology of Hirschsprung's disease (HD) is not fully understood, but recent studies have disclosed that neural cell adhesion molecule (NCAM) and glial cell line-derived neurotrophic factor (GDNF) play important roles in the formation of aganglionic bowel of Hirschsprung's disease. To evaluate the roles of NCAM and GDNF in HD, immunohistochemical analysis was performed using formalin-fixed and paraffin-embedded tissue sections. On the basis of the results, we tried to evaluate them as diagnostic markers. The specimens were obtained from 7 patients with HD who underwent modified Duhamel operation. The diagnosis was based on the clinical findings and the absence of ganglion cells in the nerve plexuses by routine microscopy. NCAM immunoreactivity was found in the nerve plexuses and scattered nerve fibers in the smooth muscle layers of ganglionic segments. In aganglionic segments, the number of NCAM positive nerve fibers in the smooth muscle layers was significantly reduced compared with ganglionic segments. In two cases the nerve plexuses in aganglionic segments, NCAM was negligible. The smooth muscle cells showed diffuse immunoreactivity for GDNF and the staining intensity was not different in the aganglionic and ganglionic segments. However, higher expression of GDNF in the nerve plexus of the ganglionic segments was noted comparing to aganglionic segments. These data suggest that both NCAM and GDNF may play important roles in pathogenesis of Hirschsprung's disease and immunohistochemical staining for NCAM can be used as an ancillary diagnostic tool for HD.

• BMB Reports
• /
• v.57 no.4
• /
• pp.167-175
• /
• 2024

Cancer progression is driven by genetic mutations, environmental factors, and intricate interactions within the tumor microenvironment (TME). The TME comprises of diverse cell types, such as cancer cells, immune cells, stromal cells, and neuronal cells. These cells mutually influence each other through various factors, including cytokines, vascular perfusion, and matrix stiffness. In the initial or developmental stage of cancer, neurotrophic factors such as nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor are associated with poor prognosis of various cancers by communicating with cancer cells, immune cells, and peripheral nerves within the TME. Over the past decade, research has been conducted to prevent cancer growth by controlling the activation of neurotrophic factors within tumors, exhibiting a novel attemt in cancer treatment with promising results. More recently, research focusing on controlling cancer growth through regulation of the autonomic nervous system, including the sympathetic and parasympathetic nervous systems, has gained significant attention. Sympathetic signaling predominantly promotes tumor progression, while the role of parasympathetic signaling varies among different cancer types. Neurotransmitters released from these signalings can directly or indirectly affect tumor cells or immune cells within the TME. Additionally, sensory nerve significantly promotes cancer progression. In the advanced stage of cancer, cancer-associated cachexia occurs, characterized by tissue wasting and reduced quality of life. This process involves the pathways via brainstem growth and differentiation factor 15-glial cell line-derived neurotrophic factor receptor alpha-like signaling and hypothalamic proopiomelanocortin neurons. Our review highlights the critical role of neurotrophic factors as well as central nervous system on the progression of cancer, offering promising avenues for targeted therapeutic strategies.

• BMB Reports
• /
• v.53 no.12
• /
• pp.646-651
• /
• 2020

Bone resorption is linked to bone formation via temporal and spatial coupling within the remodeling cycle. Several lines of evidence point to the critical role of coupling factors derived from pre-osteoclasts (POCs) during the regulation of bone marrow-derived mesenchymal stem cells (BMMSCs). However, the role of glial cell-derived neurotrophic factor (GDNF) in BMMSCs is not completely understood. Herein, we demonstrate the role of POC-derived GDNF in regulating the migration and osteogenic differentiation of BMMSCs. RNA sequencing revealed GDNF upregulation in POCs compared with monocytes/macrophages. Specifically, BMMSC migration was inhibited by a neutralizing antibody against GDNF in pre-osteoclast-conditioned medium (POC-CM), whereas treatment with a recombinant GDNF enhanced migration and osteogenic differentiation. In addition, POC-CM derived from GDNF knock-downed bone marrow macrophages suppressed BMMSC migration and osteogenic differentiation. SPP86, a small molecule inhibitor, inhibits BMMSC migration and osteogenic differentiation by targeting the receptor tyrosine kinase RET, which is recruited by GDNF into the GFRα1 complex. Overall, this study highlights the role of POC-derived GDNF in BMMSC migration and osteogenic differentiation, suggesting that GDNF regulates bone metabolism.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2002.11b
• /
• pp.140-140
• /
• 2002

Glial cell-derived neurotrophic factor (GDNF) is a potent neurotrophic factor that enhances survival of midbrain doparminergic neuron and is a member of the transforming growth factor-b superfamily. GDNF and its receptors are widely distributed in brain and are believed to be involved in the control of neuron survival, proliferation and differentiation.(omitted)

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.326.2-327
• /
• 2002

Glial cell-derived neurotrophic factor (GDNF) is a potent neurotrophic factor that enhances survival of midbrain doparminergic neuron. GDNF and its receptors are widely distributed in brain and are believed to be involved in the control of neuron survival and differentiation. In this study, we examined the effect of GDNF on proliferation and migration of Hs683 human glioma cells. GDNF markedly enhances proliferation and migration of Hs683 cells in a dose-dependent manner. (omitted)

• 한국생물공학회:학술대회논문집
• /
• 2003.04a
• /
• pp.743-746
• /
• 2003

The major pathological lesion in Parkinson's disease(PD) is selective degeneration and loss of pigmented dopaminergic neurons in substantia nigra (SN). Although the initial cause and subsequent molecular signaling mechanisms leading to the dopaminergic cell death underlying the PD process is elusive, the potent neurotrophic factors (NTFs), brain derived neurotrophic factor (BDNF) and glial cell line derived neurotrophic factor (GDNF), are known to exert dopaminergic neuroprotection both in vivo and in vitro models of PD employing the neurotoxin, MPTP. BDNF and its receptor, trkB are expressed in SN dopaminergic neurons and their innervation target. Thus, neurotrophins may have autocrine, paracrine and retrograde transport effects on the SN dopaminergic neurons. This study determined the BDNF secretion from SN dopaminergic neurons by ELISA. Regulation of BDNF synthesis/release and changes in signaling pathways are monitored in the presence of free radical donor, NO donor and mitochondrial inhibitors. Also, this study shows that BDNF is able to promote survival and phenotypic differentiation of SN dopaminergic neurons in culture and protect them against MPTP-induced neurotoxicity via MAP kinase pathway.

• Proceedings of the PSK Conference
• /
• 2003.04a
• /
• pp.223.2-224
• /
• 2003

Glial cell-derived neurotrophic factor (GDNF) is a potent neurotrophic factor that enhances survival of midbrain doparminergic neuron. GDNF and its receptors are widely distributed in brain and are believed to be involved in the control of neuron survival and differentiation. GDNF increased proliferation and migration of Hs683 human giloma and C6 rat giloma cells in a dose-dependent manner. (omitted)

• Proceedings of the PSK Conference
• /
• 2002.04a
• /
• pp.174.2-175
• /
• 2002

• The Korean Journal of Pain
• /
• v.36 no.1
• /
• pp.72-83
• /
• 2023

Background: Globally, spinal cord injury (SCI) results in a big burden, including 90% suffering permanent disability, and 60%-69% experiencing neuropathic pain. The main causes are oxidative stress, inflammation, and degeneration. The efficacy of the stem cell secretome is promising, but the role of human neural stem cell (HNSC)-secretome in neuropathic pain is unclear. This study evaluated how the mechanism of HNSC-secretome improves neuropathic pain and locomotor function in SCI rat models through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities. Methods: A proper experimental study investigated 15 Rattus norvegicus divided into normal, control, and treatment groups (30 µL HNSC-secretome, intrathecal in the level of T10, three days post-traumatic SCI). Twenty-eight days post-injury, specimens were collected, and matrix metalloproteinase (MMP)-9, F2-Isoprostanes, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and brain derived neurotrophic factor (BDNF) were analyzed. Locomotor recovery was evaluated via Basso, Beattie, and Bresnahan scores. Neuropathic pain was evaluated using the Rat Grimace Scale. Results: The HNSC-secretome could improve locomotor recovery and neuropathic pain, decrease F2-Isoprostane (antioxidant), decrease MMP-9 and TNF-α (anti-inflammatory), as well as modulate TGF-β and BDNF (neurotrophic factor). Moreover, HNSC-secretomes maintain the extracellular matrix of SCI by reducing the matrix degradation effect of MMP-9 and increasing the collagen formation effect of TGF-β as a resistor of glial scar formation. Conclusions: The present study demonstrated the mechanism of HNSC-secretome in improving neuropathic pain and locomotor function in SCI through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

• The Korean Journal of Physiology and Pharmacology
• /
• v.8 no.5
• /
• pp.245-251
• /
• 2004

The effects of fetal mesencephalic cell grafts on the restoration of nigrostriatal dopaminergic function were studied in the intrastriatal 6-hydroxydopamine-lesioned rats. Four weeks after lesioning, transplantation of ventral mesencephalic cells from embryonic day 14 fetuses showed the number of tyrosine hydroxylase (TH) positive cells and fiber outgrowth in the grafted striatum, and significantly ameliorated symptomatic motor behavior of the animals, as determined by apomorphine-induced rotation. Furthermore, in substantia nigra pars compacta (SNc), the numbers of TH + cells and fibers were markedly restored. Dopamine content of ipsilateral SNc was close to that of contralateral SNc $(91.9{\pm}9.8%)$ in the transplanted animals, while the ratio was approximately 32% in sham-grafted animals. These results indicate that grafted cells restored the activity for the dopaminergic neurons located in SNc, although they were transplanted into striatum. In addition, we showed that the implanted fetal cells expressed high level of glial cell line-derived neurotrophic factor (GDNF), suggesting that the transplanted fetal cells might serve as a dopamine producer and a reservoir of neurotrophic factors. These results may be helpful in consideration of the therapeutic transplantation at early stage of PD.