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Neuronomodulation refers to the modulation of neural conduction and synaptic transmission (i.e., the conduction process involved in synaptic transmission) of excitable neurons via changes in the membrane potential in response to chemical substances, from spillover neurotransmitters to paracrine or endocrine hormones circulating in the blood. Neuronomodulation can be direct or indirect, depending on the transduction pathways from the ligand binding site to the ion pore, either on the same molecule, i.e. the ion channel, or through an intermediate step on different molecules. The major players in direct neuronomodulation are ligand-gated or voltage-gated ion channels. The key process of direct neuronomodulation is the binding and chemoactivation of ligand-gated or voltage-gated ion channels, either orthosterically or allosterically, by various ligands. Indirect neuronomodulation involves metabotropic receptor-mediated slow potentials, where steroid hormones, cytokines, and chemokines can implement these actions. Elucidating neuronomodulation is of great significance for understanding the physiological mechanisms of brain function, and the occurrence and treatment of diseases.
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Ligandos , Neuronas/metabolismo , Transmisión Sináptica/fisiología , Canales Iónicos/metabolismo , Hormonas/metabolismoRESUMEN
@#Objective To explore the timing and safety of limited-period lung cancer surgery in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods Clinical data of of patients infected with COVID-19 undergoing lung cancer surgery (an observation group) in the Department of Thoracic Surgery of Guangdong Provincial People's Hospital, the Department of Thoracic Surgery of General Hospital of Southern Theater Command of PLA, and the Department of Cardiothoracic Surgery of the First Affiliated Hospital of Guangdong Pharmaceutical University from December 2022 to January 2023 were retrospectively analyzed and compared with patients who underwent surgery during the same period but were not infected with COVID-19 (a control group), to explore the impact of COVID-19 infection on lung cancer surgery. Results We finally included 110 patients with 73 patients in the observation group (28 males and 45 females at age of 52.62±12.80 years) and 37 patients in the control group (22 males and 15 females at age of 56.84±11.14 years). The average operation time of the observation group was longer than that of the control group, and the incidence of anhelation was higher than that of the control group (P<0.05). There were no statistcal differences in blood loss, length of hospital stay, moderate or above fever rate, degree of cough and chest pain, or blood routine between the two groups. Conclusion It is safe and feasible to perform lung cancer surgery early after recovery for COVID-19 patients with lung cancer.
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Objective: To investigate the effect of glucocorticoid on high K + induced catecholamine secretion in PC12 cells. Methods: High performance liquid chromatography with electrochemical detection were used to measure catecholamine secreted by PC12 cells. Results:(1) After PC12 cells were pretreated with various concentration of corticosterone at 37℃ for 5 min and then stimulated with various concentration of high K + for different time periods, the inhibitory effect of corticosterone on catecholamine secretion was found in a dose dependent manner. (2) When the duration of high K + treatment was prolonged, the inhibitory effect of corticosterone on catecholamine secretion tended to be attenuated. Conclusion: Glucocorticoid can rapidly inhibit the catecholamine secretion induced by high K + in PC12 cells. [
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Objective To investigate the role of steroids on the intracellular signal transduction mechanism of nongenomic effects for L 929 cells to uptake glycine. Methods The labeled glycine in L 929 cells was measured by scintillation technique. After L 929 cells were incubated with labeled glycine and steroid and/or other chemical reagents, the effects of steroids and their mechanism were determined. Results Corticosterone, aldosterone, estradiol, dexamethone and hydrocortisone inhibited glycine uptake by L 929 cells to various extents. There was no substantial difference between the effects of bovine serum album conjugated corticosterone and corticosterone 21 sulfate on glycine uptake. The inhibitor of G protein, GDP ? S, could partially block the effects of corticosterone and aldosterone. The inhibitor of phospholipase C, neomycine, did not inhibit the effect of corticosterone. The inhibitor of protein kinase C, Chelerythrine, partially blocked the effect of corticosterone. The activator of protein kinase C (phorbol 12 myristate, 13, acetate) seemed to imitate the effect of corticosterone. The activator of cAMP, Forskolin, and the inhibitor of protein kinase A, H 89 , blocked the effect of corticosterone. Conclusion The rapid inhibitory effects of steroids on glycine uptake in L 929 cells are nongenomic, and their signal transduction is through the pathway of G protein protein kinase C.
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AIM To investigate the nongenomic effects of steroids on glycine uptake in L 929 cells. METHODS L 929 cells were incubated with labeled glycine, steroids, and/or other reagents. With liquid scintillation technique, the labeled glycine in L 929 was measured. RESULTS Steroids could rapidly inhibit the glycine uptake. Action intensity of steroids was different. Effects of CORT and ALD were dose-dependent. There was no difference in effects between corticosterone 21-sulfate and B-BSA. Inhibitor for cytoplasm receptor of glucocorticoids could partially block the effect of CORT. Extracelullar Ca 2+ could influence the effect of CORT. CONCLUSION Effects of steroids on glycine uptake in L 929 cells are nongenomic. Steroids may take effect through membrane receptors. The receptors of CORT in membrane are similar to those of glucocorticoids in cytoplasm.
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The present study was undertaken by radioligand binding assay to compare the binding properties of U72099E to cytosol and synaptic plasma membrane (SPM)preparations of rat brain. The results showed that the binding of [3H]Glucocorticoids ([3H]GC) was not displaced by U72099E in cytosol but was displaced in SPM with a Ki of 32.2?1.7?mol/L-1,indicating the existence of binding sites for U72099E in plasma membrane (most probably being glucocorticoid membrane receptors, GCMR). The Ki of U72099E is close to the concentrations needed to mimic the actions of it to protect against brain injury, suggesting that GCMR may mediate the beneficial effect of U72099E.
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The effect of stress with electric tail-shock on interleukin-1 (IL-1) production by peritoneal exudate jnacrophages of C57 BL/6 mice was studied. The results showed that IL-1 level was decreased to 63.7?5.5%, 59.2?4.8%, and 61.2?3.8% of that of control 6 h, 12h, and 20h after stress, respectively (P
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The present investigation was undertaken to study the effect of hypothalamic stimulation on the pain response elicited by tail stimulation and pain-suggestive response evoked by midbrain stimulation (vocaliz-tion) in lightly anesthetized cat. In 45 hypothalamic stimulations testing its effect on CG-elicited vocalization, 22 inhibited the vocalization response, 6 facilitated it, and 17 showed no effect. In 22 hypothalamic stimu ations testing its effect on tail-elicited vocalizations, 18 inhibited the vocalization, 4 showed no effect Furthermore, in 5 spontaneously groaning cats, hypothalamic stimulations could successively inhibited the groaning. The result indicate that the hypothalamus-mid-brain continum is intimately related with pain modulation.
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In 34 hypothalamic slices of rats, spontaneous discharging of 63 paraventricular neurons was extracellulariy recorded by glass microelectrode. When the slices were perfused with artificial cerebrospinal fluid (ACSF) containing noradrenaline (NA) (10-6 mol/L), firing rates of 20 units significantly increased, those of 8 units decreased or even ceased, and those of 35 units, not affected. When low Ca2+ high Mg2+-ACSF was applied to block synaptic transmission, of 20 units which were excited by NA, 14 units still had excitatory responses and 6 units had no significant response to NA. When synaptic transmission was blocked, of 8 units which were inhibited by NA, 7 units still had inhibitory responses and only one unit had no significant response to NA. The results of this experiment strongly suggest the existence of direct effects of NA on paraventricular neurons.
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Effects of microiontophoretically applied transmitter receptor antagonists on the evoked response of “pain” units of PVN in rats by sciatic stimulation were observed. The results showed: (l)The evoked response of 7 out of 38 PVN “pain” units could be blocked by atropine (7/38); 5 out of 27 by hexamethonium; 6 out of 31 by phentolamine (6/31); and 4 out of 25 by propranolol (4/25). Seventeen out of 52 were blocked by cyproheptadine (17/52), but 3 out of 52 were augmented by cyproheptadine (3/52). (2) The evoked response of the same “pain” unit could be blocked by two antagonists: the evoked response of 2 out of 27 PVN “pain” units could be blocked by atropine and cyprohepadine; 3 out of 20 by hexamethonium and cyproheptadine; 2 out of 25 by prepamolol and cyproheptadine. These results suggest that the noxious somatic input to PVN involves 5-HT, cholinergic and adrenergic transmitter receptor mechanisms and that the convergence of various transmitter systems on PVN “pain” unit is indicated.
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Present work was undertaken to investigate the effect of destruction of different non-mediobasal hypothalamic areas on the traumatic stress responses in 64 Sprague-Dawley rats.Leg break was used as a stressor.The plasma corticosterone levels before (Bo) and 20' after the legbreak (Bs) were determined using competitive protein binding assay.The values of Bs/Bo and Bs-Bo were taken as indicators for the magnitude of the stress responses.The animals were divided into 6 groups according to injured brain areas: sham operated group, PVH injured group, PVH partially injured group, PVH minimally injured group, anterior hypothalamic-preoptic area injured group, posterior hypothalamic area injured group.Having compared statistically all Bs/Bo and Bs-Bo values of 6 groups, and on the basis of the fact that in the 4 cases of complete bilateral PVH destruction the stress response could not be entirely abolished, we conclude. (1) In traumatic stress response of conscious animals, PVH plays an important role as compared with other non-mediobasal hypothalamic areas. (2) Some CRF-containing neurons outside the PVH may also participate in the above-mentioned stress response.
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17B~estradiol. Displacement experiments showed that when RU38486 concentration reached 100~280-fold that of [3H]corticosterone, it began to inhibit [3H]corticosterone binding, while low concentration of RU38486 had no inhibitory effect.
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Unit discharges of neurons of the hypothalamic ventromedial nucleus region (HVM) and its surrounding structures including paraventricular nucleus, anterior hypothalamic area,and hypolhalamic dorsomcdial nucleus, were recorded in the ureth-ane-anesthetized and flaxidel-immobilized rats. In HVM,8 of 82 units showed periodical fluctuations in discharge rate, which could be categorized into two types: (1) With alternating active and silent phases 5 (2) with gradually waxing and waning phases. The duration of cach cycle varied from 1 to 5 minutes in different neurons. The periodicity disappeared after intraperitoneal injection of nembutal, while the average discharge rate was raised somewhat. This result suggested that the depressing pha-s of periodical activity of the HVM neuron might probably result from the inhibitory action in certain neuronal circuit, rather than from the intrinsic property of the recorded neurons. The effect of picrotoxin was contradictory. No periodical activity was noted in the 47 recorded neurons outside of the HVM.