Lateral giant (LG)-mediated escape response of crayfish is sensitized by natural traumatic events. Such sensitization has previously been shown to be associated with increased transmission between primary afferents and sensory interneurons at the cholinergic synapse of LG escape reflex circuit. In the present study, it was firstly investigated as to whether transmission is also altered at other synapses of the LG-escape reflex circuit by traumatic shock-induced sensitization. Evidence that traumatic shock also directly affects the excitability of lateral giants is now provided by the finding that traumatic shock produces a significant reduction of the time needed for LG to recruit its contralateral homologue, which is defined as commissural delay. Octopamine, a naturally occurring neuromodulator in the crayfish nerve cord, has also been shown to enhance transmission at the cholinergic synapse between primary afferents and sensory interneurons, and has been conjectured to mediate sensitization. Like traumatic shock, $octopamine\;(10^{-5}-5{\times}10^{-4}\;M)$ also enhanced the efficacy of commissural transmission between lateral giants, as indicated by a significant reduction of commissural delay. This effect was blocked by an octopamine antagonist phentolamine, suggesting a specific action of octopamine on the octopamine receptor present on LGs. These observations suggest that both traumatic shocks and octopamine may cause a rather broad alteration in the excitability of the crayfish nervous system that contributes to the sensitization of the LG escape response.
Interstitial cells of Cajal (ICC) evoke pacemaker activities in many tissues. The purpose of this study was to investigate the relationship between interstitial cell and pacemaker activity in the human ureter through the recording of spontaneous contractions. Spontaneous contractions of eight circular and longitudinal smooth muscle strips of the human ureter to acetylcholine (ACh) and/or norepinephrine (NE) were observed. Human ureteral strips were divided into proximal and distal groups, and each group was subdivided into circular and longitudinal groups. The proximal group showed spontaneous activities of 3~4 times within 5 minutes in the longitudinal group. ACh ($10^{-4}\;M$) augmented the frequency of the spontaneous contractions. The cumulative application of NE also augmented the frequency in a dose-dependent manner. The effects of NE application were inhibited by concomitant application of $10^{-5}\;M$ glibenclamide. Receptor tyrosine kinase (c-kit) staining revealed abundant ICCs only in proximal tissues. Therefore, spontaneous contractions of the human ureter might be modulated by ICC in the proximal region, and the actions might be related with the activation of cholinergic and/or adrenergic system mediated by a glibenclamide-sensitive pathway.
These days, as the average span of population's life increases, the number patients of dementia also increases. But Research on Korean medicine is stilled limited. The research evaluates the effect of the extract from Cornus officinalis S.et Z on cognitive impairment induced by scopolamine in mice. The mice were randomly divided into five groups of ten mice. The normal group was treated with only 0.9% saline. The control group was treated with scopolamine (5 mg/kg, i.p.). The positive control group was treated with tacrin. The C100, 200 group was treated with C. officinalis extracts 100, 200 mg/kg. Memory-related behaviors were evaluated using a morris water maze and a passive avoidance test. Protein levels of BDNF, p-CREB (ser133), immunohistochemistry staining, and cholinergic activities were measured in brain tissue. The effects of C. officinalis extract significantly increased acetylcholine concentration and decreased acetylcholinesterase activity. The C. officinalis extract affected memory formation. Also, to confirm expression of protein BDNF, p-CREB (ser133) in the hippocampus, the researchers observed that immunohistochemistry and western blot increased in C. officinalis extract. These results suggest that C. officinalis provides a significant neuroprotective effect against scopolamine-induced cholinergic system and cognitive impairment.
Acetylcholine receptors (AChR) including muscarinic and nicotinic AChR are widely expressed and mediate a variety of physiological cellular responses in neuronal and non-neuronal cells. Notably, a functional cholinergic system exists in oral epithelial cells, and nicotinic AChR (nAChR) mediates cholinergic anti-inflammatory responses. However, the pathophysiological roles of AChR in periodontitis are unclear. Here, we show that activation of AChR elicits increased cytosolic $Ca^{2+}([Ca^{2+}]_i)$, transient cytotoxicity, and induction of receptor activator of nuclear factor kappa-B ligand (RANKL) expression. Intracellular $Ca^{2+}$ mobilization in human gingival fibroblast-1 (hGF-1) cells was measured using the fluorescent $Ca^{2+}$ indicator, fura-2/AM. Cytotoxicity and induction of gene expression were evaluated by measuring the release of glucose-6-phosphate dehydrogenase and RT-PCR. Activation of AChR in hGF-1 cells by carbachol (Cch) induced $[Ca^{2+}]_i$ increase in a dose-dependent manner. Treatment with a high concentration of Cch on hGF-1 cells caused transient cytotoxicity. Notably, treatment of hGF-1 cells with Cch resulted in upregulated RANKL expression. The findings may indicate potential roles of AChR in gingival fibroblast cells in bone remodeling.
BACKGROUND/OBJECTIVES: It is known that the renin-angiotensin system (RAS) in the brain could regulate cognitive functions as well as blood pressure. Inhibition of RAS for the improvement of cognitive function may be a new strategy, but studies so far have mostly reported on the effects of RAS inhibition by drugs, and there is no research on cognitive improvement through RAS inhibition of food ingredients. Therefore, this study investigated the effect of curcumin on blood pressure and cognitive function and its related mechanism in spontaneously hypertensive rat/Izm (SHR/Izm). MATERIALS/METHODS: Six-week-old SHR/Izm rats were divided into 5 groups: control group (CON), scopolamine group (SCO, drug for inducing cognitive deficits), positive control (SCO and tacrine [TAC]), curcumin 100 group (CUR100, SCO + Cur 100 mg/kg), and curcumin 200 group (CUR200, SCO + Cur 200 mg/kg). Changes in blood pressure, RAS, cholinergic system, and cognitive function were compared before and after cognitive impairment. RESULTS: The SCO group showed increased blood pressure and significantly reduced cognitive function based on the y-maze and passive avoidance test. Curcumin treatments significantly improved blood pressure and cognitive function compared with the SCO group. In both the CUR100 and CUR200 groups, the mRNA expressions of angiotensin-converting enzyme (ACE) and angiotensin II receptor type1 (AT1), as well as the concentrations of angiotensin II (Ang II) in brain tissue were significantly decreased. The mRNA expression of the muscarinic acetylcholine receptors (mAChRs) and acetylcholine (ACh) content was significantly increased, compared with the SCO group. CONCLUSIONS: The administration of curcumin improved blood pressure and cognitive function in SCO-induced hypertensive mice, indicating that the cholinergic system was improved by suppressing RAS and AT1 receptor expression and increasing the mAChR expression.
Proceedings of the Korean Society for Emotion and Sensibility Conference
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1999.03a
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pp.243-248
/
1999
There is substantial evidence that anatomical connections and functional interactions exist between vestibular and autonomic systems. Heart rate variability (HRV) including mean, standard deviation, coefficient of variation (CV), power spectrum was analyzed for evaluation of the physiological role of the vestibular system on control of heart rate in rabbits. In anesthetized rabbits, electrical stimulation of the vagus nerve decreased heart rate and decreased LF/HF by increasing HF. On the cervical sympathetic nerve increased heart rate and increased LF/HF by increasing LF. Atropine, cholinergic blocker, increased heart rate and increased LF/HF by reducing HF, and propranolol, ${\beta}$-adrenergic blocker, decreased heart rate and decreased LF/HF by reducing LF> In unanesthetized rabbits, stimulation of the vestibular system induced by rotation or caloric increased heart rate and increased LF/HF by increasing LF> Also electrical stimulation of the vestibular nerve produced the same of effects as rotation or caloric in anesthetized rabbits. These results suggest that Stimulation of the vestibular system increased heart rate not by inhibiting the parasympathetic nerve but by activating the sympathetic nerve.
Objectives : To investigate the analgesic effect and its cholinergic mechanism of electroacupuncture(EA) in the rat model of collagen-induced arthritis(CIA). Methods : Immunization of male Sprague-Dawley rats with bovine typeII (CII) collagen emulsified in Freund's incomplete adjuvant, followed by a booster injection 14 days later, leads to development of arthritis in more than 70% of rats by 21 days postinjection. After three weeks of first immunization, EA stimulation(2 Hz, 0.07 mA, 0.3 ms) was delivered into Jogsamni($ST_{36}$) for 30 minutes. Analgesic effect was evaluated by tail flick latency(TFL). We compared the analgesic effect of EA with TFLs between pretreatment of normal saline and pretreatment of Atropine (1 mg/kg, intraperitoneal) and Neostigmine ($100{\mu}g/kg$, intraperitoneal) in CIA. Results : 1. TFLs were gradually decreased in CIA as increasing severity of arthritis. 2. Jogsamni($ST_{36}$) EA stimulation in CIA increased TFLs and the effect lasted for 60 minutes. 3. Increased TFLs with Jogsamni($ST_{36}$) EA stimulation were inhibited with pretreatment of atropine in CIA 4. Increased TFLs with Jogsamni($ST_{36}$) EA stimulation did not show an obvious synergistic effect with pretreatment of neostigmine in CIA. Conclusions: Jogsamni($ST_{36}$) EA showed analgesic effects in CIA. The analgesic effects of Jogsamni($ST_{36}$) EA were inhibited by atropine pretreatment and combined application of Jogsamni(ST36) EA and neostigmine did not show an synergistic effect. These observations suggest that intrinsic muscarinic cholinergic pathways represent an important modulating system in pain perception of inflammatory pain in CIA It is suggested that, the active mechanism of analgesic effect in EA may involve the release of acetylcholine in the spinal cord.
The role of the lower esophageal sphincter(LES) is characterized by the ability to maintain tone and to relax allowing the passage of a bolus. It is known that LES relaxation during swallowing may be induced by the cessation of the tonic neural excitation and the activation of non-adrenergic, non-cholinergic(NANC) inhibitory neurons. Furthermore, it is generally accepted that the relaxation of the smooth muscle is mediated primarily by the elaboration of adenosine 3',5'-cyclic monophosphate(cyclic AMP) and guanosine 3',5'-cyclic mono-phosphate(cyclic GMP) via activation of adenylate cyclase and guanylate cyclase, respectively. It is thus possible that cyclic nucleotides might be a second messenger involved in neural stimulation-induced relaxation of LES, although a relationship between relaxation and changes in cyclic nucleotides after neural stimulation has not been established. The present study was performed to define the participation of cyclic nucleotides in the relaxation of LES of dog in response to neural stimulation. Electrical field stimulation(EFS) caused relaxation of the canine isolated LES strips in a frequency-dependent manner, which was eliminated by pretreatment with tetrodotoxin$(1{\mu}M)$, but not by atropine$(100{\mu}M)$, guanethidine$(100{\mu}M)$ and indomethacin$(10{\mu}M)$. The nitric oxide synthase inhibitors, $N^G-nitro-L-arginine$, $N^G-nitro-L-arginine$ methyl ester and $N^G-monomethyl-L-arginine$ inhibited EFS-induced relaxation. Additions of sodium nitroprusside, a nitrovasodilator and forskolin, a direct adenylate cyclase stimulant, caused a dose-dependent relaxation of LES smooth muscle. Effects of sodium nitroprusside and forskolin were selectively blocked by the corresponding inhibitors, methylene blue for guanylate cyclase and N-ethylmaleimide(NEM) for adenylate cyclase, respectively. Dibutyryl cyclic AMP and dibutyryl cyclic GMP caused a concentration-dependent relaxation of the LES smooth muscle tone, which was not blocked by NEM or methylene blue, respectively. However, both NEM and methylene blue caused significant antagonism of the relaxation in LES tone in response to EFS. EFS increased the tissue cyclic GMP content by 124%, whereas it did not affect the tissue level of cyclic AMP. Based on these results, it is suggested that one of the components of canine LES smooth muscle relaxation in response to neural stimulation is mediated by an increase of cyclic GMP via the activation of guanylate cyclase. Additionally, an activation of cyclic AMP generation system was, in part, involved in the EFS-induced relaxation.
Lee, Hyung Eun;Lee, So Young;Kim, Ju Sun;Park, Se Jin;Kim, Jong Min;Lee, Young Woo;Jung, Jun Man;Kim, Dong Hyun;Shin, Bum Young;Jang, Dae Sik;Kang, Sam Sik;Ryu, Jong Hoon
Biomolecules & Therapeutics
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v.21
no.4
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pp.299-306
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2013
In the present study, we investigated the effect of ethanolic extract of the seed of Zizyphus jujuba var. spinosa (EEZS) on cholinergic blockade-induced memory impairment in mice. Male ICR mice were treated with EEZS. The behavioral tests were conducted using the passive avoidance, the Y-maze, and the Morris water maze tasks. EEZS (100 or 200 mg/kg, p.o.) significantly ameliorated the scopolamine-induced cognitive impairment in our present behavioral tasks without changes of locomotor activity. The ameliorating effect of EEZS on scopolamine-induced memory impairment was significantly reversed by a sub-effective dose of MK-801 (0.0125 mg/kg, s.c.). In addition, single administration of EEZS in normal naive mouse enhanced latency time in the passive avoidance task. Western blot analysis was employed to confirm the mechanism of memory-ameliorating effect of EEZS. Administration of EEZS (200 mg/kg) increased the level of memory-related signaling molecules, including phosphorylation of extracellular signal-regulated kinase or cAMP response element-binding protein in the hippocampal region. Also, the time-dependent expression level of brain-derived neurotrophic factor by the administration of EEZS was markedly increased from 3 to 9 h. These results suggest that EEZS has memory-ameliorating effect on scopolamine-induced cognitive impairment, which is mediated by the enhancement of the cholinergic neurotransmitter system, in part, via NMDA receptor signaling, and that EEZS would be useful agent against cognitive dysfunction such as Alzheimer's disease.
The development of the superior cervical ganglion was studied by electron microscopic method in human fetuses ranging from 40 mm to 260 mm of crown-rump length(10 to 30 weeks of gestational age). At 40 mm fetus, the superior cervical ganglion was composed of clusters of undifferentiated cell, primitive neuroblast, primitive supporting cell, and unmyelinated fibers. At 70 mm fetus, the neuroblasts and their processes were ensheated by the bodies or processes of satellite cells. The cytoplasm of the neuroblast contained rough endoplasmic reticulum, mitochondria, Golgi complex, Nissl bodies and dense-cored vesicles. As the neuroblasts grew and differentiated dense-cored vesicles moved away from perikaryal cytoplasm into developing processes. Synaptic contacts between the cholinergic axon and dendrites of postganglionic neuron and a few axosomatic synapses were first observed at 70 mm fetus. At 90 mm fetus the superior cervical ganglion consisted of neuroblasts, satellite cells, granule-containing cells, and unmyelinated nerve fibers. The ganglion cells increased somewhat in numbers and size by 150 mm fetus. Further differentiation resulted in the formation of young ganglion cells, whose cytoplasm was densely filled with cell organelles. During next prenatal stage up to 260 mm fetus, the cytoplasm of the ganglion cells contained except for large pigment granules, all intracytoplasmic structures which were also found in mature superior cervical ganglion. A great number of synaptic contact zones between the cholinergic preganglionic axon and the dendrites of the postganglionic neuron were observed and a few axosomatic synapses were also observed. Two morphological types of the granule-containing cells in the superior cervical ganglion were first identified at 90 mm fetus. Type I granule-containing cell occurred in solitary, whereas type II tended to appeared in clusters near the blood capillaries. Synaptic contacts were first found on the solitary granule-containing cell at 150 mm fetus. Synaptic contacts between the soma of type I granule-containing cells and preganglionic axon termials were observed. In addition, synaptic junctions between the processes of the granule-containing cells and dendrites of postganglionic neuron were also observed from 150 mm fetus onward. In conclusion, superior cervical ganglion cells and granule-containing cells arise from a common undifferentiated cell precursor of neural crest. The granule-containg cells exhibit a local modulatory feedback system in the superior cervical ganglion and may serve as interneurons between the preganglionic and postganglionic cells.
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