The hypothalamo-pituitary-gonadal hormone axis is centrally controlled by a complex regulatory network of excitatory and inhibitory signals, that is dormant during infantile and juvenile periods and activated at puberty. The kisspeptins are the peptide products of the KiSS-1 gene and the endogenous agonists for the G protein-coupled receptor 54(GPR54). Although KiSS-1 was initially discovered as a metastasis suppressor gene, a recent evidence suggests the KiSS-1/GPR54 system is a key regulator of the reproductive system. Yet the actual role of the KiSS-1/GPR54 system in the neuroendocrine control of gonadotropin secretion remains largely unexplored, the system could be the first missing link in the reproductive hormonal axis. Central or peripheral administration of kisspeptin stimulates the hypothalamic-pituitary-gonadal axis, increasing circulating gonadotropin levels in rodents, sheep, monkey and human models. These effects appear likely to be mediated via the hypothalamic GnRH neuron system, although kisspeptins may have direct effects on the anterior pituitary gland. The loss of function mutations of the GPR54(GPR54-/-) have been associated with lack of puberty onset and idiopathic hypogonadotropic hypogonadism(IHH). So kisspeptin infusion may provide a novel mechanism for HPG axis manipulation in disorders of the reproductive system.
Kim, Kee-Soon;Shin, Hong-Kee;Kim, Jin-Hyuk;Lee, Ae-Joo;Kang, Suck-Han
The Korean Journal of Physiology
/
v.23
no.1
/
pp.151-167
/
1989
The present study was undertaken to investigate modification in electrophysiological characteristics of cat dorsal horn cells resulting from carrageenin-induced inflammation. The followings were studied; 1) the time-course of changes in responses of the WDR (wide dynamic range) cell 1-3h after subcutaneous injection of carrageenin in its receptive field; 2) the responses of the same dorsal hern cells before and after induction of inflammation; 3) the effect of inflammation on the responsiveness of dorsal horn neurons to algogens (bradykinin & potassium); and 4) the effect of inflammation on the activity of WDR cell following administration of indomethacin and clonidine. Though responses of WDR neuron were increased dramatically during first 1h, the maximal enhancement was observed 3h after induction of inflammation especially by repetitive light tactile stimulus. Following carrageenin injection the majority of WDR neurons (10/15 units) showed enhanced responses to all the mechanical stimuli while in 3 cases responsiveness were intensified during activation by one tactile stimulus (brush or pressure). One cell was unaffected by inflammation and in another case the response was enhanced only to noxious stimulus. Five of 9 cells that could initially be driven by noxious stimulus were activated more strongly by same stimulus and even by tactile stimulus (pressure) following inflammation. In 2 cases neurons were sensitized only to noxious stimulus whereas in another 2 cells that did not show enhanced responses to noxious stimulus responses to light tactile stimulus (pressure) appeared after inflammation. Of 16 LT cells tested 6 responded to squeeze while 4 showed the characteristics of WDR cell following inflammation. No modification in responsiveness was recognized in 3 cells whereas response to only brush was enhanced in another 3 neurons. Following carrageenin injection responses of LT cell to bradykinin or $K^{+}$ were not altered whereas those of WOR neurons to bradykinin or $K^{+}$ were suppressed in 22.2% and 33.3% of cases, respectively. In two of 8 activity of HT cells were inhibited by bradykinin while in five of 8 responsiveness to $K^{+}$ were rather enhanced by inflammation. In the rest inflammation was ineffective. In inflammation-induced animal the receptive field of LT cell was not changed whereas those of WDR cell and HT cell were tremendously expanded. The enhanced responses of WDR neurons to mechanical stimuli resulted from inflammation were suppressed by intravenously injected indomethacin and clonidine suggesting that postaglandin is involved in inflammation-induced sensitization of these cells. The involvement of peripheral and central mechanisms in the modification in responsiveness of dorsal horn cells in the carrageenin-induced inflammation was discussed.
Kim, Tae Geun;Seo, Jeehye;Kim, Yangho;Yun, Byoung-Ju;Chang, Yongmin
Progress in Medical Physics
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v.26
no.2
/
pp.72-78
/
2015
Organic solvents are known toxic effects like vertigo, behavioral obstacle, distracting, and peripheral neuropathy in neuron areas. However, there have been few studies how neurotoxic solvents-exposed workers are affected by the cognitive load of preceding working memory tasks. Therefore, we used fMRI as to measure the neural correlates of working memory impairment in occupational workers who had from chronic exposure to organic solvent. Twenty-nine solvent-exposed workers were included in this study. Each participant concluded the verbal N-back tasks (1- and 2-back) during the fMRI acquisition. Within-group analyses showed fronto-parietal networks were active in each condition. Direct comparisons between 1- and 2-back showed higher activation during the 2-back than 1-back. We found that increased activation of these regions at lower task demand is associated with increased cost of implementing.
Seo, Dong-Man;Kim, Sang-Jeong;Lim, Won-il;Kim, Jun;Kim, Chong-Whan
Journal of Chest Surgery
/
v.31
no.5
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pp.441-450
/
1998
The medullospinal tract cells are known to play an important role in the control of the cardiovascular activities. To clarify the modes of action of the neurotransmitters on these cells, glutamate, GABA(${\gamma}$-aminobutyric acid) and bicuculline were applicated iontophoretically into the rostral ventrolateral medulla in adult cats anesthetised with ${\alpha}$-chloralose. Followings are the results obtained : 1. The spontaneous activities of the cardiac-related neurons in rostral ventrolateral medulla (RVLM) were increased by the glutamate and decreased by the GABA. 2. Bicuculline, an antagonist of GABA, alone didn't increase the frequency of the action potentials, but could reverse the cellular response to the GABA, simultaneously applicated. 3. GABA seemed to decrease the peak as well as the basal discharge of the neurons in RVLM, but hardly changed their periodicities. 4. The cellular responses of RVLM evoked by the peripheral nerve stimulation could be inhibited by the iontophoretically released GABA. In conclusion, GABA seemed to act as an inhibitory neurotransmitter on the cardiac- related neurons in RVLM of the cats anesthetized with ${\alpha}$-chloralose. But the maintenance of the periodicities of these cells after the application of bicuculline suggested that the afferent activity of the baroreceptor didn't play a key role in the spontaneous activities of the RVLM neurons.
As the average life span have been lengthened and the rate of senile population have been raised, chronic degenerative diseases incident to aging has been increased rapidly and become a social problem. With this social background, recently, the facts that oxygen radicals(OR) have toxic effects on Central Nervous System and Peripheral Nervous System and cause neuropathy such as Parkinson's Disease, Alzheimer Disease have been turned out, and accordingly lots of studies on the mechanism of the toxic effects of OR on nerves, the diseases caused by OR and the approaches to curing the diseases have been made. The purpose of this study is to examine the toxic effects caused by Glucose Oxidase(GO) and the effects of herbal extracts such as Chilbokyeum(CBY) on the treatment of the toxic effects. For this purpose, experiments with the cultured cell from the cerebrums of new born mice were done. The results of these experiments were as follows. 1. GO, a oxygen radical, decreased the survival rate of the cultured cells on NR assay and MTT assay 2. GO, a oxygen radical, increased lipid peroxidation and the amount of LDH. 3. CBY have efficacy of decreasing lipid peroxidation. 4. CBY have efficacy of decreasing the amount of LOH. From the above results, It is concluded that Chilbokyeum has marked efficacy as a treatment for the damages caused in the GO-mediated oxidative process. And Chilbokyeum is thought to have certain pharmacological effects on controlling over aging and treating Dementia. Further clinical study of this pharmacological effects of Chilbokyeum should be complemented.
Human mesenchymal stem cells(hMSC), that have been reported to be present in bone marrow, adipose tissues, dermis, muscles and peripheral blood, have the potential to differentiate along different lineages including those forming bone, cartilage, fat, muscle and neuron. Therefore, hMSC are attractive candidates for cell and gene therapy. The optimal conditions for hMSC expansion require medium supplemented with fetal bovine serum(FBS). Some forms of cell therapy will involve multiple doses, raising a concern over immunological reactions caused by medium-derived FBS proteins. Previously, we have shown that hADSC can be cultured in human serum(HS) during their isolation and expansion, and that they maintain their proliferative capacity and ability for multilineage differentiation and promote engraftment of peripheral blood-derived CD34 cells mobilized from bone marrow in NOD/SCID mice. In this study we determined whether hADSC grown in HS maintain surface markers expression similar with cells grown in FBS during culture expansion and compared gene expression profile by Affymetrix microarray. Flow cytometry analysis showed that HLA-DR, CD117, CD29 and CD44 expression in HS-cultured hADSC during culture expansion were similar with that in FBS-cultured cells. However, the gene expression profile in HS-cultured hADSC was significantly different from that in FBS-cultured cells. Therefore, these data indicated that HS-cultured hADSC should be used in vivo animal study of hADSC transplantation for direct extrapolation of preclinical data into clinical application.
The total-bodies of 10 week-old Sprague-Dawley rats were irradiated with single doses 4.5 and 7.5 Gy, respectively. The effects on plasma and sciatic nerve platelet-derived growth factor(PDGF) concentrations and sciatic nerve PDGF ${\alpha}$ -and ${\beta}$ -receptors densities were examined up to 10 days post-treatment. There was no consistent significant variation in the plasma and sciatic nerve PDGF concentrations in time over the period of study between 4.5 and 7.5 Gy groups. Plasma PDGF concentrations were significantly reduced to 58% of control values between 5 and 10 days with 4.5 Gy and to 51% of control values as percentage of control values between 5 and 10 days with 7.5 Gy after irradiation, respectively(p<0.05). Sciatic nerve PDGF concentrations were increased to 118% of control values at 1 day with 4.5 Gy and to 130% of control values at 1 day with 7.5 Gy after irradiation, respectively(p>0.05). After irradiation, the levels of PDGF ${\alpha}$ -receptor protein density were reduced to 33% of control values at 2 days with 4.5 Gy and to 50% at 2 days with 7.5 Gy, while the levels of PDGF ${\beta}$-receptor protein density were reduced to maximally 26% of control values at 2 days with 4.5 Gy and to 27% at 2 days with 7.5 Gy, respectively, but both initial decreased levels of those were increased subsequently after 2 days following irradiation. These results suggest that the radiation-induced alteration of plasma and sciatic nerve PDGF concentrations, and sciatic nerve PDGF ${\alpha}$ -and ${\beta}$ -receptors densities may be involved in the pathogenesis of bone marrow stem cell and peripheral neuron damages.
Purpose : It had been suggested that pain arising from deep somatic body regions influences neural activity within periaqueductal gray(PAG) of midbrain via distinct spinal pathways. Aspirin is one of the popular non-steroidal anti-inflammatory drugs used in the management of pain. Fos expression was used as a marker for neuronal activity throughout central neurons following painful peripheral stimulation. This study was prepared to investigate changes of c-Fos immunoreactivity in midbrain by deep pain and effects of aspirin. Methods : Male Sprague-Dawley rats were injected with 0.1 mL of 5% formalin in the plantar muscle of the right hindpaw. For experimental group II, aspirin was injected intravenously before injection of formalin. An aspirin-untreated group was utilized as group I. Rats were sacrificed at 0.5, 1, 2, 6 and 24 hours after formalin injection. Rat's brains were removed and sliced in rat brain matrix. Brain slices were coronally sectioned at interaural 1.00-1.36 mm. Serial sections were immunohistochemically reacted with polyclonal c-Fos antibody. The numbers of c-Fos protein immunoreactive neurons in ventrolateral periaqueductal gray(VLPAG) and dorsomedial periaqueductal gray(DMPAG) were counted and analyzed statistically with Mann-Whitney U tests. Results : Higher numbers of c-Fos protein immunoreactive neurons were found in VLPAG. In both VLPAG and DMPAG of formalin-treated group, the numbers of c-Fos protein immunoreactive neurons were significantly higher at all time points than the formalin-untreated group, which peaked at two hours. The numbers of c-Fos immunoreactive neuron of the aspirin-treated group were less compared to the aspirin-untreated group at each time point. Conclusion : These results provide some basic knowledge in understanding the mechanism of formalin-induced deep somatic pain and the effects of aspirin.
GABA is an inhibitory neurotransmitter in central nervous system and produce sedative, antianxiety and muscle reaxing effects via $GABA_A$ receptor or $GABA_B$ receptor. Recently it is known that GABA is widely distributed throughout peripheral organs and may playa physiological role in certain organ. The vas deferens is innervated by species-difference. These study, therefore, was performed to investigate the mode and the mechanism of action of GABA on the norepiniphrine-, ATP- and electric stimulation-induced contraction of vas deferens of rat. Sprague-Dawley rats were sacrificed by cervical dislocation. The smooth muscle strips were isolated from the prostastic portion and were mounted in the isolated muscle bath. PSS in the bath was aerated with 95/5%-$O_2/CO_2$ at $33^{\circ}C$. Muscle tensions were measured by isometric tension transducer and were recorded by biological recording system. 1. GABA, muscimol, a $GAB_A$ agonist, and baclofen, a $GABA_B$ agonist inhibited the electric field stimulation(EFS, 0.2Hz, 1mSec, 80 V, monophasic square wave)-induced contraction with a rank order of potency of GABA greater than baclofen greater than muscimol. 2. The inhibitory effect of GABA was antagonized by delta aminovaleric acid(DAVA), a $GABA_B$ antagonist, but not by bicuculline, a $GABA_A$ mtagonist. 3. The inhibitory effect of baclofen was antagonized by DAVA, but the effect of muscimol was not antagonized by bicuculline. 4. Exogenous norepinephrine(NE) and ATP contracted muscle strip concentration dependently, but the effect of acetylcholine was negligible : and GABA did not affect the NE-and ATP-induced contractions. 5. GABA, baclofen and muscimol did not affect basal tone, and GABA did not affect the NE-and ATP-induced contractionsm 6. EFS-induced contraction was including 2 distinctable components. The first phasic component was inhibited by beta gamma-methylene ATP(mATP), a desensitizing agent of APT receptor and the second tonic component was reduced by pretreatment of reserpine(3 mg/Kg, IP). 7. GABA inhibited the EFS-induced contraction of reserpinized strips, but not the mATP-treated strips. These results suggest that in the prostatic portion of the rat vas deferens, adrenergic and purinergic neurotransmissions are exist, and GABA inhibits the release of ATP via presynaptic $GABA_B$ receptor on the excitatory neurons.
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