• BMB Reports
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• 제57권4호
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• pp.167-175
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• 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.

• 생명과학회지
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• 제28권2호
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• pp.240-246
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• 2018

원심성, 구심성 교감신경 신호는 고혈압 및 심부전의 발생과 밀접한 관련이 있다. 혈관 내 카테터를 이용한 교감신경절제술(RDM)은 난치성 고혈압의 대체치료로 시행되어 왔다. 시술과 관련하여 장기간 신장의 안정성에 대해서는 보고가 있었으나 단기간 심근의 안정성에 대한 연구 결과는 없었다. 저자들은 RDN 시술로 인한 교감신경차단 후 염증성 심근손상이 발생할 수 있음을 가정하여 실험으로 검증하고자 하였다. 25마리의 암컷돼지를 3군으로 나누고-정상대조군(n=5), Sham군(n=5), RDN 시술군(n=15)-RDN 시술군을 시술 후 sacrifice 시기에 따라 다시 세분하였다-시술 후 즉시 sacrifice한 RDN-0 (n=5), 시술 1주 후 sacrifice한 RDN-1 (n=5), 시술 2주 후 sacrifice한 RDN-2 (n=5). 조영제의 영향을 배제하기 위해 설정했던 Sham군과 정상대조군 간에는 의미있는 차이를 보이지 않았다. $IL-1{\beta}$, $TNF-{\alpha}$ 등의 염증 싸이토카인은 시술 1주 후 증가하여 2주째 감소하였다. 항염증 싸이토카인 IL-10은 시술 직후부터 증가하여 2주째 감소하였다. Inflammasome에 의해 위험신호(danger signal)를 전달받고 활성화되는 Caspase-1 및 inflammasome을 매개하는 도메인 ASC는 시술 직후 활성화되어 발현이 증가하였고 2주까지 지속되었다. 그러나 caspase-1을 매개할 것으로 추정되었던 NLRP3 inflammasome의 발현은 의미있는 차이를 보이지 않았다. RDN 시술에 의한 교감신경차단은 caspase-1, $IL-1{\beta}$ 등의 활성화에 의해 염증성 심근손상을 초래할 수 있으며 RDN 시술 후에는 그 위험성을 고려해야 하겠다. NLRP3 외에 다른 NLRP inflammasome pathway의 관련성에 대한 추가연구가 필요하다.

• The Korean Journal of Physiology
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• 제27권2호
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• pp.185-197
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• 1993

The rostral ventrolateral medulla (RVLM) includes vasopressor neurons, which transmit activation signals to the intermediolateral nucleus (IML) of the spinal cord, where the preganglionic sympathetic nucleus is located, to raise arterial blood pressure (BP). However, controversy exists as to the possible depressor area in the RVLM and the pathway involved. The present study persued evidence far the location of depressor neurons and the pathway by simultaneously observing changes in BP and the firing rate (FR) of cardiovascular neurons (CVNs) in the RVLM during the somatosympathetic reflex (SSR) elicited by peripheral nerve stimulation, since CVNs are known to contribute to the generation of the sympathetic nerve discharge. In 42 cats, anaesthetized with $\alpha-chloralose$, single unit recording was performed, using carbon filament electrodes inserted into the RVLM, enabling estimation of the post R wave unit histogram (PR-UNlT) and the spike triggered average of sympathetic nerve discharge (STA-SND), allowing identification of CVNs. Antidromic stimulation of spinal $T_2$ segment was followed to determine whether the identified CVN projects axonal endings to the spinal cord (reticulospinal neuron). The sciatic nerve was electrically stimulated at $A\delta-intensity$ (1 mA, 0.1 ms), 1 Hz and C-intensity (10 mA, 0.5 ms), 20 Hz to elicit the depressor, and pressor responses of the SSR, respectively. Simultaneous measurement of CVN firing rate was made. Experimental results are summarized as follows. 1) 20 out of 98 CVNs had axonal projections to the spinal cord and 17 out of 98 CVNs showed FR changes during SSR. 2) Response patterns of FR and BP during SSR were classified into 8 types. 3) These 8 different response patterns could be further classified into those from pressor and depressor neurons. These results demonstrate that some CVNs were identifiable as reticulospinal neurons responding to anti-dromic stimulation and that CVNs operating as depressor neurons as well as pressor neurons exist in the RVLM, both of which are involved with SSR mediation. Therefore, evidence was found that an independent depressor pathway might be involved in the mediation of SSR.

• 한국임상수의학회지
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• 제28권4호
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• pp.403-407
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• 2011

A form of polycystic ovary (PCO) resembling some aspects of the human PCO syndrome (PCOS) can be induced in rats by a single injection of estradiol valerate (EV). An increase in sympathetic outflow to the ovary precedes, by several weeks, the appearance of cysts, suggesting the involvement of a neurogenic component in the pathology of this ovarian dysfunction. To test the hypotheses that the change in sympathetic tone is related to an augmented production of hippocampal and/or ovarian nerve growth factor (NGF), and that this abnormally elevated production of NGF contributes to the induction of PCOS induced by EV. The animals were sacrificed after PCOS induction and the ovaries and hippocampus were sectioned and compared to the normal control. The expression of NGF was measured by immunohistochemical staining and Western blot analysis in the ovaries and hippocampus. EV-induced PCOS showed significant increase of ovarian NGF expression. Immunohistochemical expression of NGF was confined to the follicular cells and interstitial cells. Hippocampal NGF expression was not significantly changed. In conclusion EV-induced PCOS was related to the ovarian sympathetic activation which was mediated by NGF.

• 동의신경정신과학회지
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• 제20권2호
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• pp.85-99
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• 2009

Objectives : This study aimed to understand the influence of acupuncture on the human body by comparing changes within human bodies before and after people in normal health are treated with acupuncture at the acupoints HT7 and PC9, which are related to mental functions. Methods : The study was performed from January 3, 2008 to March 5, 2008 on 60 healthy males and females in their 20s. HRV, EEG, skin conductance response, respiration and peripheral skin temperature were measured for 5 minutes before acupuncture simulation was applied to the acupoints HT7 and PC9. During 20 minutes of acupuncture treatment, the same items were continuously measured to determine whether there had been any changes, and they were then measured for 5 minutes after the removal of the acupuncture needles in order to implement a comparative analysis. Results : 1. The HRV measurement showed that in the course of before, during and after acupuncture stimulation, heart rate, HF and HF norm decreased significantly (P<0.05) at HT7. LF, LF norm, and LF/HF ratio increased significantly (P>0.05), while heart rate, HF and HF norm decreased significantly (P<0.05) at PC9. 2. Skin conductance response increased significantly (P<0.05) at PC9 during and after the acupuncture simulation periods, compared with the pre acupuncture period. 3. the peripheral skin temperature increased significantly (P<0.05) both at HT7 and PC9 in the course of before, during and after acupuncture stimulation. 4. Compared with the pre-acupuncture period, respiration rate increased both at HT7 and at PC9 during and after the acupuncture simulation periods, but not in a statistically significance. 5. In the EEG measurement, when compared with the pre-acupuncture period at HT7, mid ${\beta}$ wave decreased significantly (P<0.05) during acupuncture treatment. Compared with the measurements during acupuncture treatment at PC9, low ${\beta}$ wave increased significantly (P<0.05) after the acupuncture needles were removed. Conclusions : When acupuncture treatment is applied at the acupoints HT7 and PC9, the activation of parasympathetic nerves decreases and the activation of sympathetic nerves increases in the HRV measurement. It was determined that PC9 makes the sympathetic nerves become highly activated in a skin conduction response. The effect of stability in the brain wave seemed to bo shown at HT7 than PC9.

• 한국정밀공학회:학술대회논문집
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• 한국정밀공학회 2005년도 춘계학술대회 논문집
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• pp.1929-1932
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• 2005

We investigated the activities of autonomic nervous system during foot bathing. The effect of foot bathing was evaluated for four subjects by observing the characteristic of heart rate variability and bodily temperatures. The foot bathing was done with a commercial foot spa (Duches Co.) utilizing the four functional modes of the spa for two different temperatures of $35^{\circ}C\;and\;40^{\circ}C$. The four functional modes were clam, vibration, air bubbles, and both vibration and air bubbles. The experimental results showed that the temperature of foot and that of face right after foot bathing were not that different from each other. But, for heart rate variability, the activation of parasympathetic nerve showed distinctive increase at $40^{\circ}C$ of water temperature. In the analysis of heart rate variability for different functional modes, the change was not distinctive for different modes at $35^{\circ}$ of water temperature. However, at $40^{\circ}C$, the activation of sympathetic nerve showed distinctive increases with the increase in the complexity of functional modes.

• Journal of Acupuncture Research
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• 제28권2호
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• pp.107-116
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• 2011

Objectives : This study was performed to investigate the effects of fixed-intensity and varied-intensity electroacupuncture on heart rate variability in healthy people with stress task. Methods : Forty healthy subjects were randomly assigned to either group A or group B or C. Group A received fixed-intensity electroacupuncture(F-EA) at $ST_{36}$ and $ST_{37}$. After 1 week wash out period to prevent overlapping residual effects, they received varied-intensity electroacupuncture(V-EA) in which the intensity was changed every two minutes based on individual heart rate variability at the same points. Group B received the treatments in reverse order. Group C received no intervention as a control group. Results : Control group showed a significant increase of LF and LF/HF during the 2nd working memory task, while both F-EA and V-EA did not. In addition, V-EA showed a significant increase of HF during 2nd rest while F-EA did not. Conclusions : These results suggest that F-EA and V-EA can inhibit sympathetic activation more than control group and that V-EA can enhance parasympathetic activation more than F-EA.

• The Korean Journal of Physiology and Pharmacology
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• 제18권1호
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• pp.47-53
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• 2014

In this study, we propose that diprophylline exerts bidirectional modulation (BM) on the isolated rat jejunal segment depending on its contractile state. The results supported the hypothesis. Diprophylline ($20{\mu}M$) exerted stimulatory effects on the contractility of jejunal segment in six low contractile states while inhibitory effects in six high contractile states, showing the characteristics of BM. Diprophylline-induced stimulatory effect was significantly blocked by atropine, indicating the correlation with cholinergic activation. Diprophylline-induced inhibitory effect was partially blocked by phentolamine, propranolol, and L-N-Nitro-Arginine respectively, indicating their correlation with sympathetic activation and nitric oxide-mediated relaxing mechanisms. Diprophylline-induced BM was abolished by tetrodotoxin or in a $Ca^{2+}$ free condition or pretreated with tyrosine kinase inhibitor imatinib, suggesting that diprophylline-induced BM is $Ca^{2+}$ dependent, and that it requires the presence of enteric nervous system as well as pacemaker activity of interstitial cells of Cajal. Diprophylline significantly increased the reduced MLCK expression and myosin extent in constipation-prominent rats and significantly decreased the increased MLCK expression and myosin extent in diarrhea-prominent rats, suggesting that the change of MLCK expression may also be involved in diprophylline-induced BM on rat jejunal contractility. In summary, diprophylline-exerted BM depends on the contractile states of the jejunal segments, requires the presence of $Ca^{2+}$, enteric nervous system, pacemaker activity of interstitial cells of Cajal, and MLCK-correlated myosin phosphorylation. The results suggest the potential implication of diprophylline in relieving alternative hypo/hyper intestinal motility.

• 대한수의학회지
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• 제38권3호
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• pp.508-517
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• 1998

There is evidence that the sympathetic nervous system exerts a control on thyroid function via an adrenergic innervation of thyroid cells. Although it is clear that the inhibitory effects of catecholamines result from an activation of ${\alpha}_1$-adrenoceptors, the mechanisms involved in ${\alpha}_1$-stimulation are not fully understood. The effects of methoxamine and protein kinase C (PKC) activator on the release of thyroxine ($T_4$) from mouse thyroid were studied to clarify the role of PKC in the regulation of $T_4$ release in vitro. The glands were incubated in the medium, samples of the medium were assayed for $T_4$ by EIA kits. Methoxamine inhibited the TSH-stimulated $T_4$ release. This inhibition was reversed by prazosin, an ${\alpha}_1$-adrenergic antagonist. Futhermore, the inhibitory effect of methoxamine on the $T_4$ release stimulated by TSH was prevented by chloroethylclonidine, an ${\alpha}_{1b}$-adrenoceptor antagonist, but not by WB4101, an ${\alpha}_{1a}$-adrenoceptor antagonist. Also methoxamine inhibited the forskolin-, cAMP- or IBMX-stimulated $T_4$ release. These inhibition were reversed by PKC inhibitors, such as staurosporine and $H_7$. PMA, a PKC activator, completely inhibited the TSH-stimulated $T_4$ release, and its inhibition was reversed by staurosporine and $H_7$, but not by chelerythrine. R59022 (a diacylglycerol kinase inhibitor), like methoxamine, also inhibited the TSH-stimulated $T_4$ release, and its inhibition was also reversed by staurosporine. The present study suggests that methoxamine inhibition of $T_4$ release from mouse thyroid can be induced by activation of the ${\alpha}_{1b}$-adrenoceptors and that it is mediated through the ${\alpha}_1$-adrenoceptor-stimulated PKC formation.

• International Journal of Oral Biology
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• 제38권3호
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• pp.121-126
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• 2013

Tumor necrosis factor alpha ($TNF{\alpha}$) is a multifunctional inflammatory cytokine that regulates various cellular and biological processes. Increased levels of $TNF{\alpha}$ have been implicated in a number of human diseases including diabetes and arthritis. Sympathetic nervous system stimulation via the beta2-adrenergic receptor (${\beta}2AR$) in osteoblasts suppresses osteogenic activity. We previously reported that $TNF{\alpha}$ upregulates ${\beta}2AR$ expression in murine osteoblastic cells and that this modulation is associated with $TNF{\alpha}$ inhibition of osteoblast differentiation. In our present study, we explored whether $TNF{\alpha}$ induces ${\beta}2AR$ expression in human osteoblasts and then identified the downstream signaling pathway. Our results indicated that ${\beta}2AR$ expression was increased in Saos-2 and C2C12 cells by $TNF{\alpha}$ treatment, and that this increase was blocked by the inhibition of NF-${\kappa}B$ activation. Chromatin immunoprecipitation and luciferase reporter assay results indicated that NF-${\kappa}B$ directly binds to its cognate elements on the ${\beta}2AR$ promoter and thereby stimulates ${\beta}2AR$ expression. These findings suggest that the activation of $TNF{\alpha}$ signaling in osteoblastic cells leads to an upregulation of ${\beta}2AR$ and also that $TNF{\alpha}$ induces ${\beta}2AR$ expression in an NF-${\kappa}B$-dependent manner.