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

• Restorative Dentistry and Endodontics
• /
• v.45 no.2
• /
• pp.20.1-20.14
• /
• 2020

Objectives: To minimize the tooth sensitivity caused by in-office bleaching, many dentists use non-steroidal anti-inflammatory drugs and topical desensitizing gels containing potassium nitrate and sodium fluoride. This study aimed to evaluate the influence of these substances on inflammation and the expression of substance P and calcitonin gene-related peptide in pulp nerve fibers. Materials and Methods: Seventy-two rats were divided into 6 groups as follows: GI, control; GII, only dental bleaching; GIII, only ibuprofen; GIV, ibuprofen administered 30 minutes before and after the bleaching treatment and every 12 hours until the analysis; GV, only topical application of a desensitizing agent; and GVI, topical application of a desensitizing agent before dental bleaching. Placebo gel was applied to the upper left jaw and the bleaching agent was applied to the upper right jaw in all groups. Subsequently, the groups were divided into 3 subgroups based on the time of analysis: 0, 24, and 48 hours after bleaching (n = 8). The rats were euthanized and the maxillae were processed and evaluated by histopathological and immunohistochemical analyses. The data were analyzed using the Kruskal-Wallis test, followed by the Dunn test (p < 0.05). Results: In the bleaching groups, the inflammatory process and expression of neuropeptides decreased over time. The animals in which a desensitizing agent was applied showed better results within 24 hours. Conclusions: The use of a desensitizing agent had positive effects on inflammation and pain-related neuropeptide expression, minimizing the painful effects of dental bleaching treatment.

• The Korean Journal of Physiology and Pharmacology
• /
• v.12 no.5
• /
• pp.217-223
• /
• 2008

To directly test if elevated glucocorticoids are required for fasting-induced regulation of growth hormone (GH)-releasing hormone (GHRH), GHRH receptors (GHRH-R) and ghrelin receptors (GHS-R) expression, male rats were bilaterally adrenalectomized or sham operated. After 7 days, animals were fed ad libitum or fasted for 48 h. Bilateral adrenalectomy increased hypothalamic GHRH to 146% and decreased neuropeptide Y (NPY) mRNA to 54% of SHAM controls. Pituitary GHRH-R and GHS-R mRNA levels were decreased by adrenalectomy to 30% and 80% of shamoperated controls. In shamoperated rats, fasting suppressed hypothalamic GHRH (49%) and stimulated NPY (166%) mRNA levels, while fasting increased pituitary GHRH-R (391%) and GHS-R (218%) mRNA levels. However, in adrenalectomized rats, fasting failed to alter pituitary GHRH-R mRNA levels, while the fasting-induced suppression of GHRH and elevation of NPY and GHS-R mRNA levels remained intact. In fasted adrenalectomized rats, corticosterone replacement increased GHRH-R mRNA levels and intensified the fasting-induced decrease in GHRH, but did not alter NPY or GHS-R response. These data suggest that elevated glucocorticoids mediate the effects of fasting on hypothalamic GHRH and pituitary GHRH-R expression, while glucocorticoids are likely not the major determinant in fasting-induced increases in hypothalamic NPY and pituitary GHS-R expression.

• Korean Journal of Veterinary Research
• /
• v.42 no.1
• /
• pp.7-20
• /
• 2002

This study deals with the distribution and morphological study of the neurons with the neuropeptide Y (NPY) in developing chick brain. The developing brains of Korean native chicks at embryonic days 8 (E8), E10, E12, E14, E16, E18, and E20 were used. The chicks were perfused with 4% paraformaldehyde through the left ventricle and aorta. The brains were removed and transferred into 30% sucrose, and then cut in a cryostat into $60{\mu}m$ in thickness. The sections were immunostained with free-floating and avidin-biotin complex (ABC) methods. The numerous neurons with NPY were first observed in nucleus rotundus of diencephalon at E8. In particular, neurons in nucleus rotundus had the well-developed processes. At E12, the neurons with NPY were distributed widely in diencephalon; nucleus septalis lateralis, medialis, nucleus magnocelluaris preopticus dorsalis, medialis, ventralis, nucleus preopticus medialis, nucleus dorsolateralis anterior thalami pars magnocellularis, and nucleus paraventricularis magnocellularis (paraventricular nucleus) except nucleus rotundus. From E12 to E20, positive neurons were oval-shaped, changed gradually into the spherical- and multipolar-shaped. The shapes of processes were also omnidirectional and the number of those were less than in telencephalon. As the chicks developed, the morphology of neurons with NPY showed the tendency to increase in their sizes and numbers.

• Food Science and Biotechnology
• /
• v.17 no.4
• /
• pp.700-704
• /
• 2008

Anti-obesity effects of $\beta$-cyclodextrin in obese C57BL/6J mice induced by a high fat diet (HD) were observed. The administration of $\beta$-cyclodextrin reduced the gain of body weight, abdominal fat, liver weight, the lipid deposits of hepatocytes and the size of adipocytes in the HD group. In serum analysis, the total and low-density lipoprotein-cholesterols were significantly decreased in the $\beta$-cyclodextrin-supplemented HD group than in the HD group. However, high-density lipoprotein-cholesterol was not changed in these groups. In hypothalamic homogenates, the decrease of neuropeptide Y and increase of $\alpha$-melanocyte stimulating hormone were detected in the $\beta$-cyclodextrin-supplemented HD group compared to that in the HD group. These effects of $\beta$-cyclodextrin were similar to those of Garcinia cambogia, which is widely used as a natural anti-obesity product. These results suggest that $\beta$-cyclodextrin has anti-obesity effects through the lowering of the abdominal fat pad and inhibits the central effects of hunger.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.30 no.5
• /
• pp.937-942
• /
• 2001

The present study was conducted to identify the mechanism about the regulation of appetite by examining the expression patterns of vasoactive intestinal peptide in the hypothalamus of either fasted for 24 hours or anorexia mutant mouse. In order to investigate expression pattern of the vasoactive intestinal peptide, immunohisto-chemistry was employed along with reverse transcription polymerase chain reaction (RT-PCR) and dot blotting. Immunohistochemistry has shown that level of expression of vasoactive intestinal peptide and appetite-suppessing neuropeptide, was lower in the suprachiasmatic nucleus (SCN) and higher in the paraventricular nucleus (PVN) of the anorexia mutant group than in the comparable regions in the control group. This pattern was repeated in the fasting group, which also showed lower and higher levels of vasoactive intestinal peptide expression in the SCN and PVN respectively, In contrast, the vasoactive intestinal peptide mRNA level in the entire hypothalamus via RT-PCR and dot blotting was similar in the fasting and control groups, while it was significantly increased in the anorexia mutant group.

• Journal of Life Science
• /
• v.29 no.1
• /
• pp.118-122
• /
• 2019

Oxytocin (Oxt) and vasopressin (Avp) are mainly synthesized in neuronal cells of the hypothalamus and are released from the posterior pituitary. The structure and sequences of Oxt and Avp genes imply that they are closely related and that they are the result of a duplication event during evolution. A previous study suggested that a small regulatory microRNA (miRNA), miR-24, regulated Oxt after binding. However, it is not clear whether this miRNA can modulate Avp simultaneously. The aim of the present study was to investigate putative targeting miRNAs of Avp, including miR-24. Targeted candidate miRNA oligonucleotides were transfected into COS-7 cells to elucidate the binding activity of miRNAs and Avp using dual-luciferase assays. The luciferase assay showed that only miR-24 displayed elevated binding activity with Avp as compared to a control and other candidate miRNAs. Transfection with seed mutants of Avp and miR-24 inhibitors clearly showed that miR-24 can directly bind to the Avp gene. These results provide new insight into the regulatory mechanism of neurohypophysial hormones by a single miRNA.

• Molecules and Cells
• /
• v.42 no.4
• /
• pp.301-312
• /
• 2019

Post-transcriptional regulation underlies the circadian control of gene expression and animal behaviors. However, the role of mRNA surveillance via the nonsense-mediated mRNA decay (NMD) pathway in circadian rhythms remains elusive. Here, we report that Drosophila NMD pathway acts in a subset of circadian pacemaker neurons to maintain robust 24 h rhythms of free-running locomotor activity. RNA interference-mediated depletion of key NMD factors in timeless-expressing clock cells decreased the amplitude of circadian locomotor behaviors. Transgenic manipulation of the NMD pathway in clock neurons expressing a neuropeptide PIGMENT-DISPERSING FACTOR (PDF) was sufficient to dampen or lengthen free-running locomotor rhythms. Confocal imaging of a transgenic NMD reporter revealed that arrhythmic Clock mutants exhibited stronger NMD activity in PDF-expressing neurons than wild-type. We further found that hypomorphic mutations in Suppressor with morphogenetic effect on genitalia 5 (Smg5) or Smg6 impaired circadian behaviors. These NMD mutants normally developed PDF-expressing clock neurons and displayed daily oscillations in the transcript levels of core clock genes. By contrast, the loss of Smg5 or Smg6 function affected the relative transcript levels of cAMP response element-binding protein B (CrebB) in an isoform-specific manner. Moreover, the overexpression of a transcriptional repressor form of CrebB rescued free-running locomotor rhythms in Smg5-depleted flies. These data demonstrate that CrebB is a rate-limiting substrate of the genetic NMD pathway important for the behavioral output of circadian clocks in Drosophila.

• The Korean Journal of Physiology and Pharmacology
• /
• v.26 no.4
• /
• pp.255-262
• /
• 2022

Oxytocin is a neuropeptide produced primarily in the hypothalamus and plays an important role in the regulation of mammalian birth and lactation. It has been shown that oxytocin has important cardiovascular protective effects. Here we investigated the effects of oxytocin on vascular reactivity and underlying the mechanisms in human umbilical vein endothelial cells (HUVECs) in vitro and in rat aorta ex vivo. Oxytocin increased phospho-eNOS (Ser 1177) and phospho-Akt (Ser 473) expression in HUVECs in vitro and the aorta of rat ex vivo. Wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), inhibited oxytocin-induced Akt and eNOS phosphorylation. In the rat aortic rings, oxytocin induced a biphasic vascular reactivity: oxytocin at low dose (10^-9-10^-8 M) initiated a vasorelaxation followed by a vasoconstriction at high dose (10^-7 M). L-NAME (a nitric oxide synthase inhibitor), endothelium removal or wortmannin abolished oxytocin-induced vasorelaxation, and slightly enhanced oxytocin-induced vasoconstriction. Atosiban, an oxytocin/vasopressin 1a receptor inhibitor, totally blocked oxytocin-induced relaxation and vasoconstriction. PD98059 (ERK1/2 inhibitor) partially inhibited oxytocin-induced vasoconstriction. Oxytocin also increased aortic phospho-ERK1/2 expression, which was reduced by either atosiban or PD98059, suggesting that oxytocin-induced vasoconstriction was partially mediated by oxytocin/V1aR activation of ERK1/2. The present study demonstrates that oxytocin can activate different signaling pathways to cause vasorelaxation or vasoconstriction. Oxytocin stimulation of PI3K/eNOS-derived nitric oxide may participate in maintenance of cardiovascular homeostasis, and different vascular reactivities to low or high dose of oxytocin suggest that oxytocin may have different regulatory effects on vascular tone under physiological or pathophysiological conditions.

• Clinical and Experimental Pediatrics
• /
• v.65 no.4
• /
• pp.172-181
• /
• 2022

Pubertal onset is known to result from reactivation of the hypothalamic-pituitary-gonadal (HPG) axis, which is controlled by complex interactions of genetic and nongenetic factors. Most cases of precocious puberty (PP) are diagnosed as central PP (CPP), defined as premature activation of the HPG axis. The cause of CPP in most girls is not identifiable and, thus, referred to as idiopathic CPP (ICPP), whereas boys are more likely to have an organic lesion in the brain. ICPP has a genetic background, as supported by studies showing that maternal age at menarche is associated with pubertal timing in their offspring. A gain of expression in the kisspeptin gene (KISS1), gain-of-function mutation in the kisspeptin receptor gene (KISS1R), loss-of-function mutation in makorin ring finger protein 3 (MKRN3), and loss-of-function mutations in the delta-like homolog 1 gene (DLK1) have been associated with ICPP. Other genes, such as gamma-aminobutyric acid receptor subunit alpha-1 (GABRA1), lin-28 homolog B (LIN28B), neuropeptide Y (NPYR), tachykinin 3 (TAC3), and tachykinin receptor 3 (TACR3), have been implicated in the progression of ICPP, although their relationships require elucidation. Environmental and socioeconomic factors may also be correlated with ICPP. In the progression of CPP, epigenetic factors such as DNA methylation, histone posttranslational modifications, and non-coding ribonucleic acids may mediate the relationship between genetic and environmental factors. CPP is correlated with short- and long-term adverse health outcomes, which forms the rationale for research focusing on understanding its genetic and nongenetic factors.