• Biomedical Science Letters
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• v.11 no.3
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• pp.375-382
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• 2005

This study aimed to investigate whether nociceptin is implicated in the, trigeminovascular responses to electrical stimulation of trigeminal ganglion in rats. An open cranial window was prepared on the right parietal bone of male Sprague-Dawley rats. Trigeminovascular system was stimulated by electrical stimulation of trigeminal ganglion (ETS; 5ms, 5Hz, 3V). Neonatal capsaicin treatment was performed with subcutaneous administration of capsaicin (50mg/kg) within the first 24 hours after birth. Changes in regional cerebral blood flow were continuously measured through the cranial window by laser-Doppler flowmetry, and the expression of nociceptin-like immunoreactivity was determined by immunohistochemistry. ETS caused increases in regional blood flow of pial arteriole in a voltage-dependent manner. ETS markedly and voltage-dependently increased the expression of nociceptin-like immunoreactivity in dura mater ipsilateral rather than contralateral to ETS. The nociceptin-like immunoreactivity was markedly reduced by pretreatments with calcitonin gene-related peptide(8-37) ($CGRP_{8-37},\;a\;CGRP_1$ receptor antagonist), L-733060 (a $NK_1$ receptor antagonist), and $[Nphe^1]$ nociceptin(1-13)$NH_2$ (a selective and competitive nociceptin receptor antagonist) as well as by neonatal capsaicin treatment. These results suggest that the electrical stimulation of trigeminal ganglion causes prominent expression of nociceptin within dura mater, in which not only neuropeptides inducing substance P and CGRP but also nociceptin are implicated in the trigeminovascular responses to electrical trigeminal ganglion stimulation.

• Molecules and Cells
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• v.40 no.3
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• pp.186-194
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• 2017

A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in mammal. We investigated here a possible involvement of central NELL2 in regulating feeding behavior and metabolism. In situ hybridization and an immunohistochemical approach were used to determine expression of NELL2 as well as its colocalization with proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the rat hypothalamus. To investigate the effect of NELL2 on feeding behavior, 2 nmole of antisense NELL2 oligodeoxynucleotide was administered into the lateral ventricle of adult male rat brains for 6 consecutive days, and changes in daily body weight, food, and water intake were monitored. Metabolic state-dependent NELL2 expression in the hypothalamus was tested in vivo using a fasting model. NELL2 was noticeably expressed in the hypothalamic nuclei controlling feeding behavior. Furthermore, all arcuatic POMC and NPY positive neurons produced NELL2. The NELL2 gene expression in the hypothalamus was up-regulated by fasting. However, NELL2 did not affect POMC and NPY gene expression in the hypothalamus. A blockade of NELL2 production in the hypothalamus led to a reduction in daily food intake, followed by a loss in body weight without a change in daily water intake in normal diet condition. NELL2 did not affect short-term hunger dependent appetite behavior. Our data suggests that hypothalamic NELL2 is associated with appetite behavior, and thus central NELL2 could be a new therapeutic target for obesity.

• Molecular & Cellular Toxicology
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• v.4 no.1
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• pp.31-44
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• 2008

The forced swim test (FST) is the most widely used model for assessing potential antidepressant activity. Although it has been shown that lateral septum is involved with the FST-related behavior, it is not clear whether antidepressant treatments could alter the FST-induced gene expression profile in the lateral septum. In the present study, the gene expression profiles in response to FST and reboxetine pretreatment were observed in the lateral septum of rats. Reboxetine is known as a most selective serotonin norepinephrine reuptake inhibitor. In addition, we compared the changes in gene expression profile between reboxetine response and nonresponse groups, which were determined by counting FST-related behavior. After FST, lateral septum from controls and reboxetine pretreated group were dissected and gene expression profiles were assessed using an Affymetrix microarray system containing 15,923 genes. Various genes with different functions were changed in reboxetine response group compared with reboxetine nonresponse group, In particular, pleiotrophin, orexin receptor 2, serotonin 2A receptor, neuropeptide Y5 receptor and thyroid hormone receptor $\beta$ were decreased in reboxetine response group, but Lim motif-containing protein kinase 1 (Limk1) and histone deacetylase 1 (HDAC1) were increased. Although further studies are required for direct roles of these genes in reboxetine response, the microarray may provide tools to find out potential target genes and signaling pathways in antidepressant response.

• Proceedings of the KSAR Conference
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• 2001.03a
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• pp.47-47
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• 2001

The neuropeptide vasopressin (VP) is a nine- amino acid hormone synthesized as preprohormone in the cell bodies of hypothalamic magnocellular neurons. The tumor in magnocellular neurons of the hypothalamus is associated with disfunctions of the cell bodies, leading to the diabetes insipidus. In order to study with the diabetes insipidus caused by a defect in VP synthesis and its secretion, we have produced the transgenic mice regulated by vasopressin promoter inserted to SV40 T antigen coding sequence (pVPSV.IGR2.1). One transgenic line expressing high levels of SV40 T antigen was propagated. The founder and all transgene positive adult animals have appeared with shorten mortality or apparent phenotypic abnormalities, including immune complex disease, and eventually die between 4 and 8 months of age. The mRNA and protein of SV40T antigen transgene were detected in brain of fetus as well as in brain, spleen, lung and lymph node in moribund at the age of 20 weeks. Histological analysis of transgenic mice showed that tumor developed in brain similar to primitive neuroectodermal tumors (PNET) in man. We also detected lymphomas in spleen and lymph node, and consequent tumor formation in various tissues of the transgenic mice. In pVPSV.IGR2.1, 21% mice showed brain tumor (PNET) at 5 weeks and 100% mice showed brain tumor after 15 weeks. In addition, Expression of apoptosis related genes (Bcl-28 & Bax) was increased over their age in mice with PNET as compared to control mice. Apoptosis related gene expression might be deregulated in mice with brain tumor. However, transgenic mice were not developed with the diabetes insipidus. These mice represent the first disease model to exhibit primitive neuroectodermal tumor in brain, as well as a unique model system for exploring the cellular pathogenesis of lymphomas.

• Ocean and Polar Research
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• v.38 no.1
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• pp.81-88
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• 2016

In many fish species, including Nile tilapia (Oreochromis niloticus), gonadal development occurs at the expense of stored energy and nutrients. Therefore, reproductive systems are inhibited by limited food supply. It has been well established that reproductive function is highly sensitive to both metabolic status and energy balance. Nothing is known about the possible mediated connection between energy balance and reproduction. Kisspeptin, a neuropeptide product of the Kiss gene has emerged as an essential gatekeeper of reproduction and may be possibly be linked to energy balance and reproduction in non-mammalians. Thus, in this study, the effect of fasting (10 days) on the expression of kisspeptin and the gonadotropin-releasing hormone (GnRH) gene were assessed in Nile tilapia (male and female) using qRT-PCR. In addition, plasma levels of estradiol-$17{\beta}$ ($E_2$) and 11-ketotestosterone (11-KT) in adult tilapia were measured by ELISA. In male tilapia, fasting reduced Kiss2 and GnRH I mRNA expression in the brain and 11-KT level in comparison with the fed tilapia (p < 0.05). In females, however, there were no significant differences in GnRH I mRNA expression and $E_2$ between fish subjected to fasting and those fed (p > 0.05). These data indicate the impact of nutritional states on kisspeptin as a potential regulatory mechanism for the control of reproduction in male Nile tilapia.

• Restorative Dentistry and Endodontics
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• v.30 no.6
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• pp.470-476
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• 2005

The purpose of this Study was to invest)gate the function or calcitonin gene-related peptide (CGRP) in regulatory mechanism of pulpal microcirculation with the aim of elucidating neurogenic inflammation. Experiments were performed on twelve cats under general anesthesia. CGRP was administered through the femoral vein to see the systemic Influence and through the external carotid artery to see the local effect. Sympathetic nerve to the dental pulp was stimulated electrically and pulpal blood flow (PBF) was measured with a laser Doppler flowmeter on the canine teeth to the drug administration. The paired variables of control and experimental data were compared by paired t-test and differences with p < 0.05 were considered statistically significant. Systemic administration of CGRP $(0.3{\mu}g/ka)$ exerted decreases in systemic blood pressure and caused changes in PBF with an initial increase i311owed by decrease and a move marked second increase and decrease. Close intra-arterial (i.a.) injection of CCRP $(0.03{\mu}g/kg)$ resulted in slight PBF increase. The effect of CGRP resulted in no significant increase in PBF in the presence of $CGRP_{8-37}$. The electrical stimulation of the sympathetic nerve alone resulted in PBF decreases. The j.a. administration of CGRP following the electrical stimulation of the sympathetic nerve compensated the decreased PBF. Therefore, CGRP effectively blocked the sympathetic nerve stimulation-induced PBF decrease. Results of the present study have provided evidences that even though the local vasodilatory function of CGRP are weak, CCRP is effectively involved in blocking the vasoconstriction caused by sympathetic nerve stimulation in the feline dental pulp.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.1
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• pp.91-97
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• 2018

Objective: A 14-d trial was conducted to determine the effects of feeding corn naturally contaminated with aflatoxin $B_1$ ($AFB_1$) on growth performance, apparent ileal digestibility, serum hormones levels and gene expression of $Na^+$, $K^+-ATPase$ in ducklings. Methods: A total of 704 ducklings were blocked on the basis of sex and body weight (BW), and then allocated randomly to one of the following two treatments: i) CON, basal diet and ii) $AFB_1$, diets with 100% of normal corn replaced with $AFB_1$ contaminated corn. There were 22 pens per treatment and 16 birds per pen. The concentration of $AFB_1$ was 195.4 and $124.35{\mu}g/kg$ in the contaminated corn and $AFB_1$ diet, respectively. Results: The $AFB_1$ decreased average daily gain, average daily feed intake, d 7 BW, final BW in the whole trial, and feed conversion ratio (FCR) during d 8 to 14 and d 1 to 14 by 10% to 47% (p<0.05), while FCR during d 1 to 7 was increased (p<0.05). $AFB_1$ did not affect mortality to 7 d of age, and then increased to 5.8% from 8 to 14 d of age (p<0.01). Apparent ileal gross energy digestibility was reduced by $AFB_1$, whereas apparent ileal digestibility of dry matter, nitrogen, and amino acid was improved (p<0.01). Feeding $AFB_1$ diets increased serum concentration of leptin and insulin-like growth factors-1 (IGF-1) (p<0.05), but had no effect on neuropeptide Y, ghrelin, cholecystokinin-8 or insulin (p>0.05). Dietary treatments did not influence relative expression of jejunal $Na^+$, $K^+-ATPase$ gene (p>0.05). Conclusion: Taken together, feeding corn naturally contaminated with $AFB_1$ reduced growth performance, improved apparent ileal digestibility, and affected serum leptin and IGF-1 in ducklings from d 1 to 14.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.14
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• pp.5895-5900
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• 2014

Background: Metabolic syndrome (MS) is a cluster of complicated disorders caused by the interactive influencing factors of heredity and environment, which predisposes to many cnacers. Results from epidemic research indicate that stress is tightly related to the pathogenesis of MS and neoplasia. This paper aims to investigate the association between psychological stress and MS with respect to the tumor necrosis factor alpha (TNF${\alpha}$) and neuropeptide Y (NPY) genes in the Han and Hui ethnic groups. Methods: All subjects for this case-control study matched strict enrollment criteria (nationality, gender and age) and lived in the city of Wu Zhong of Ningxia Province in China. The enrolled group contained 102 matched pairs of Hui ethnic individuals and 98 matched pairs of Han ethnic individuals. Enrolled subjects completed the general Symptom Checklist-90 (SCL-90). The TNF${\alpha}$-308G/A variant and NPYrs16147 polymorphism were detected in case (81 males, 119 females) and control (81 males, 119 females) groups by polymerase chain reaction (PCR) amplification. Results: Nine factors of the SCL-90 were found to be statistically different (p<0.05) between case and control groups. The homozygous mutant genotype (AA) and the mutant allele (A) of the TNF${\alpha}$-308G/A gene were less frequently observed in the control population compared to the case group. The odds ratio (95% confidence interval) in "Allele" for MS was 2.28 (1.47-3.53), p=0.0001, while "OR" was 1.11 (0.83-1.47), p=0.15, for the NPYrs16147 gene polymorphism. Conclusions: Psychological stress has been positively associated with MS. A previous study from our group suggested there were differences in the level of psychological stress between Hui and Han ethnic groups. Furthermore, we found that the stress-related TNF${\alpha}$ gene was associated with MS for both Han and Hui ethnic groups. In contrast, NPY may be a possible contributor to MS and associated cancer for the Han ethnic group.

• The Journal of Dong Guk Oriental Medicine
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• v.8 no.1
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• pp.117-131
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• 1999

Yangkyuksanhoa-tang is frequently used for cerebrovascular accident(CVA). The present study was performed to investigate the effect of Yangkyuksanhoa-tang on the peri vascular immunoreactive nerve fiber of the basilar artery after experimentally induced subarachnoid hemorrhage(SAH). Sprague Dawley rats weighing between 350-400g were used. The SAH induced by injection of the fresh autologus heart blood(0.3-0.4ml) into the cisterna magna through the posterior atlanto-occipital membrane. Sample group was given a $3.3m{\ell}/kg/day$ of Yangkyuksanhoa-tang extracts for 2 days after SAH. The experimental animals divided into 48hrs after SAH. The changes of perivascular immunoreactive nerve fiber was examined by using indirect immunofluorescence method. The meshlike perivascular nerve fiber appeared in the basilar artery of normal rats. In basilar artery of SAH elicitated rat, the distribution of calcitonin gene-related peptide (CGRP)-immunoreactivity(IR) and vasoactive intestinal polypeptide(VIP)-IR of the perivascular nerve fiber were remarkably diminished, also dopamine beta hydroxylase(DBH)-IR, neuropeptide Y(NPY)-IR and serotonin-IR were diminished. In SAH elicitated rat with Yangkyuksanhoa-tang treatment, the CGRP-IR and VIP-IR degree were repaired as well as normal rat's, but DBH-IR, NPY-IR and serotonin-IR had no changes. These results provide the basic data to investigate the effect of Yangkyuksanhoa-tang on the vasospasm after SAH.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.4
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• pp.497-505
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• 2012

To determine the effects of Banggihwanggi-tang(BGHGT) on obesity, the obesity-related factors[gastrin, calcitonin gene related peptide(CGRP), serotonin, ghrelin, obestatin, glucagon-like peptide-1(GLP-1), insulin, orexin, leptin] were investigated in the stomach, pancreas, brain of mice by immunohistochemical(IHC) methods for 4 weeks. The change of body weight was more reduced in BGHGT administered group than that of control group. The IHC density of the gastrin and CGRP positive cells on pylorus was higher in BGHGT administered group than that of control group. The number of ghrelin immunoreactive cells on stomach was lower in BGHGT administered group than that of control group. The IHC of GLP-1 positive cells did not observe in the stomach of BGHGT administered groups. The IHC density of GLP-1 in the pancreas was lower in BGHGT administered group than that of control group. The IHC density of insulin positive cells in the pancreas was lower in BGHGT administered group than that of control group. The IHC density of orexin positive neurons in the diencephalon was slightly higher in BGHGT administered group than that of control group. The IHC density of NPY and leptin positive neurons was slightly higher in BGHGT administered group than that of control group. The IHC density of serotonin positive neurons was higher in BGHGT administered group than that of control group. Therefore, we conclude that BGHGT activates appetite inhibitor through appetite related enteroendocrine cells and neuropeptides in stomach, pancreas and brain, and this activation may also be responsible for the inhibition of feeding behavior.