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Prolactin sensitive galanin neurons in the medial preoptic area
Abstracts
OF
The work was supported by HAS Postdoctoral Research Fellowship Program for MCS, OTKA K100319 and KTIA_NAP_B_13-2-2014-0004 Program. doi:10.1016/j.npep.2017.02.056
DP
The importance of sensory-immune interactions in gastritis has recently been emphasized with special focus on Transient Receptor Potential Vanilloid 1 and Ankyrin 1 (TRPV1, TRPA1) ion channels. They are mainly localized on capsaicin-sensitive sensory nerves, activated by several spices and inflammatory substances, and mediate thermo and pain sensation, neurogenic inflammation. Since their presence on several non-neuronal cells is well-described but their functional relevance is unknown, we investigated TRPV1 and TRPA1 expressions in the human gastric mucosa at mRNA and protein levels, as well their alterations in gastritis. Gastric biopsies were collected during gastroscopy. Non-inflamed control, chronic gastritis with or without intestinal metaplasia (IM+, IM-), chronic active gastritis and chronic reactive gastropathy samples were selected after histopathological assessment. TRPV1 and TRPA1 relative gene expressions were measured by quantitative polymerase chain reaction (RT-qPCR), receptor localizations were determined by immunohistochemistry. TRPV1 and TRPA1 were both detectable in the human gastric mucosa at mRNA and protein levels confirming their local synthesis. TRPV1 showed higher expression by both RT-qPCR and immunohistochemistry compared to TRPA1. TRPV1 and TRPA1 immunopositivities were localized to the epithelial cells of the mucosal glands. TRPV1 gene expressions were significantly lower in chronic active gastritis and reactive gastropathy (relative quantities 0.24 and 0.62, respectively), whereas it was not altered in IM + and IM- gastritis patients. TRPA1 expression did not significantly change in any group. Further experiments using rodent models of gastritis are in progress to elucidate the functional relevance of these locally expressed receptors.
Wu and his coworkers showed parenting-induced Fos positive galanin neurons in the medial preoptic area. Selective ablation of these neurons resulted in cessation of the parental behavior and emergence of pup-directed aggression. We established that preoptic galanin neurons contain oxytocin. We demonstrated by double labeling that pSTAT5 appears 2 hours after suckling in galanin neurons in the anterior commissural nucleus of the preoptic area, but not in galanin neurons in the lateral part of the preoptic area. Using retrograde tracing techniques we detected that the TIP39 neurons from the posterior intralaminar thalamic complex project to medial preoptic area. By fluorescent immunohistochemistry we revealed TIP39 fibers closely appose Fos-expressing neurons in the medial preoptic area. Electron microscopic immunohistochemistry showed that TIP39 terminals make synaptic contacts on the somata of galanin neurons in the medial preoptic area. In conclusion, we demonstrated that galanin neurons controlling parental behavior also contain oxytocin. The anterior commissural nucleus is responsive to prolactin. Finally, galanin neurons may get suckling information from TIP39 neurons of the posterior intralaminar thalamic complex.
RO
Zsuzsanna Helyesa,d; aDepartment of Phamacology and Pharmacotherapy, Szentagothai Research Centre, University of Pécs, Hungary; bFirst Department of Internal Medicine, Medical and Health Center, University of Pécs, Hungary; c Department of Pathology, University of Pécs, Hungary; dMTA-PTE NAP B Pain Research Group, Pécs, Hungary; eSzentagothai Research Centre, University of Pécs, Hungary
145
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BLOCKADE OF NEUROPEPTIDE Y2 RECEPTOR REGULATES GENE EXPRESSION IN PATHWAYS OF LIPID METABOLISM IN HEPG2 CELLS
CO
RR
doi:10.1016/j.npep.2017.02.055
P7
Gedeon
Neuropeptide Y(NPY)/NPY2 receptor(NPY2R) is involved in the stress-induced visceral obesity in mice. We have previously reported the association between 5'-flanking region of NPY2R gene SNPs and plasma HDL-cholesterol levels in healthy subjects. Plasma HDLcholesterol levels were significantly different in subjects with each SNPs (rs6857530; GGb GAb AA or rs6857715; TTb TCb CC). The luciferase activity was detected in HepG2 but not in macrophage differentiated from THP-1cells when used pGL3-basic including 5'NPY2R with rs6857530GG+ rs6857715TT. The aim of the study is to elucidate further the mechanism underlying this association. After confirming that the sequences included heterozygous rs6857530(G/A) and rs6857715(T/C) in both cells, we compared the effect of NPY+/□NPY2R antagonist BIIE on comprehensive gene expression in cultured HepG2 or macrophage using microarray. In 47,400 transcripts, 863 were up-regulated by BIIE (N1.5-fold) and 559 were down-regulated (b0.67-fold) in HepG2. In macrophage, 377 were up-regulated and 229 were down-regulated. Among 77 gene ontology categories regulated by BIIE in HepG2 (P-valueb0.001), chylomicron remodeling, negative regulation of cholesterol or sterol transport were noted in up-regulated genes. In 44 pathways regulated by BIIE (Pb0.01), they included vitamin B12/HDL metabolism in up-regulated genes, and sterol responsive element binding protein signaling and cholesterol biosynthesis in down-regulated genes. Taken together, NPY might inhibit HDL and stimulate VLDL production in the liver through NPY2R, suggesting a new therapeutic target of dyslipidemia in subjects with specified NPY2R SNPs.
EC
Support: TÁMOP 4.1.1.C-13/1/KONV-2014-0001; Richter Talentum Fundation, KTIA_NAP_13-1-2013-0001.
Hidesuke Kaji, Masayo Nagai, Akiko Hamaue, Maiko Mori; University of Hyogo, Akashi, Japan
PROLACTIN SENSITIVE GALANIN NEURONS IN THE MEDIAL PREOPTIC AREA
UN
Melinda Cservenáka,b, Éva R. Szabóa,b, Viktor Kisc, Arpád Dobolyia,b; a Laboratory of Neuromorphology, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary; b Laboratory of Molecular and Systems Neurobiology, Institute of Biology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest, Hungary; cDepartment of Anatomy, Cell and Developmental Biology, Institute of Biology, Eötvös Loránd University, Budapest, Hungary Intracellular signaling pathway for prolactin involves phosphorylation of the signal transducer and activator of transcription 5 proteins. We confirmed previous studies that 2 hours suckling resulted in a widespread induction of pSTAT5 in some forebrain regions such as the arcuate nucleus, the para- and periventricular nuclei, the medial preoptic area, the bed nucleus of the stria terminalis, and the medial amygdala.
doi:10.1016/j.npep.2017.02.057
OF
The work was supported by HAS Postdoctoral Research Fellowship Program for MCS, OTKA K100319 and KTIA_NAP_B_13-2-2014-0004 Program. doi:10.1016/j.npep.2017.02.056
DP
The importance of sensory-immune interactions in gastritis has recently been emphasized with special focus on Transient Receptor Potential Vanilloid 1 and Ankyrin 1 (TRPV1, TRPA1) ion channels. They are mainly localized on capsaicin-sensitive sensory nerves, activated by several spices and inflammatory substances, and mediate thermo and pain sensation, neurogenic inflammation. Since their presence on several non-neuronal cells is well-described but their functional relevance is unknown, we investigated TRPV1 and TRPA1 expressions in the human gastric mucosa at mRNA and protein levels, as well their alterations in gastritis. Gastric biopsies were collected during gastroscopy. Non-inflamed control, chronic gastritis with or without intestinal metaplasia (IM+, IM-), chronic active gastritis and chronic reactive gastropathy samples were selected after histopathological assessment. TRPV1 and TRPA1 relative gene expressions were measured by quantitative polymerase chain reaction (RT-qPCR), receptor localizations were determined by immunohistochemistry. TRPV1 and TRPA1 were both detectable in the human gastric mucosa at mRNA and protein levels confirming their local synthesis. TRPV1 showed higher expression by both RT-qPCR and immunohistochemistry compared to TRPA1. TRPV1 and TRPA1 immunopositivities were localized to the epithelial cells of the mucosal glands. TRPV1 gene expressions were significantly lower in chronic active gastritis and reactive gastropathy (relative quantities 0.24 and 0.62, respectively), whereas it was not altered in IM + and IM- gastritis patients. TRPA1 expression did not significantly change in any group. Further experiments using rodent models of gastritis are in progress to elucidate the functional relevance of these locally expressed receptors.
Wu and his coworkers showed parenting-induced Fos positive galanin neurons in the medial preoptic area. Selective ablation of these neurons resulted in cessation of the parental behavior and emergence of pup-directed aggression. We established that preoptic galanin neurons contain oxytocin. We demonstrated by double labeling that pSTAT5 appears 2 hours after suckling in galanin neurons in the anterior commissural nucleus of the preoptic area, but not in galanin neurons in the lateral part of the preoptic area. Using retrograde tracing techniques we detected that the TIP39 neurons from the posterior intralaminar thalamic complex project to medial preoptic area. By fluorescent immunohistochemistry we revealed TIP39 fibers closely appose Fos-expressing neurons in the medial preoptic area. Electron microscopic immunohistochemistry showed that TIP39 terminals make synaptic contacts on the somata of galanin neurons in the medial preoptic area. In conclusion, we demonstrated that galanin neurons controlling parental behavior also contain oxytocin. The anterior commissural nucleus is responsive to prolactin. Finally, galanin neurons may get suckling information from TIP39 neurons of the posterior intralaminar thalamic complex.
RO
Zsuzsanna Helyesa,d; aDepartment of Phamacology and Pharmacotherapy, Szentagothai Research Centre, University of Pécs, Hungary; bFirst Department of Internal Medicine, Medical and Health Center, University of Pécs, Hungary; c Department of Pathology, University of Pécs, Hungary; dMTA-PTE NAP B Pain Research Group, Pécs, Hungary; eSzentagothai Research Centre, University of Pécs, Hungary
145
P8
TE
BLOCKADE OF NEUROPEPTIDE Y2 RECEPTOR REGULATES GENE EXPRESSION IN PATHWAYS OF LIPID METABOLISM IN HEPG2 CELLS
CO
RR
doi:10.1016/j.npep.2017.02.055
P7
Gedeon
Neuropeptide Y(NPY)/NPY2 receptor(NPY2R) is involved in the stress-induced visceral obesity in mice. We have previously reported the association between 5'-flanking region of NPY2R gene SNPs and plasma HDL-cholesterol levels in healthy subjects. Plasma HDLcholesterol levels were significantly different in subjects with each SNPs (rs6857530; GGb GAb AA or rs6857715; TTb TCb CC). The luciferase activity was detected in HepG2 but not in macrophage differentiated from THP-1cells when used pGL3-basic including 5'NPY2R with rs6857530GG+ rs6857715TT. The aim of the study is to elucidate further the mechanism underlying this association. After confirming that the sequences included heterozygous rs6857530(G/A) and rs6857715(T/C) in both cells, we compared the effect of NPY+/□NPY2R antagonist BIIE on comprehensive gene expression in cultured HepG2 or macrophage using microarray. In 47,400 transcripts, 863 were up-regulated by BIIE (N1.5-fold) and 559 were down-regulated (b0.67-fold) in HepG2. In macrophage, 377 were up-regulated and 229 were down-regulated. Among 77 gene ontology categories regulated by BIIE in HepG2 (P-valueb0.001), chylomicron remodeling, negative regulation of cholesterol or sterol transport were noted in up-regulated genes. In 44 pathways regulated by BIIE (Pb0.01), they included vitamin B12/HDL metabolism in up-regulated genes, and sterol responsive element binding protein signaling and cholesterol biosynthesis in down-regulated genes. Taken together, NPY might inhibit HDL and stimulate VLDL production in the liver through NPY2R, suggesting a new therapeutic target of dyslipidemia in subjects with specified NPY2R SNPs.
EC
Support: TÁMOP 4.1.1.C-13/1/KONV-2014-0001; Richter Talentum Fundation, KTIA_NAP_13-1-2013-0001.
Hidesuke Kaji, Masayo Nagai, Akiko Hamaue, Maiko Mori; University of Hyogo, Akashi, Japan
PROLACTIN SENSITIVE GALANIN NEURONS IN THE MEDIAL PREOPTIC AREA
UN
Melinda Cservenáka,b, Éva R. Szabóa,b, Viktor Kisc, Arpád Dobolyia,b; a Laboratory of Neuromorphology, Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary; b Laboratory of Molecular and Systems Neurobiology, Institute of Biology, Hungarian Academy of Sciences and Eötvös Loránd University, Budapest, Hungary; cDepartment of Anatomy, Cell and Developmental Biology, Institute of Biology, Eötvös Loránd University, Budapest, Hungary Intracellular signaling pathway for prolactin involves phosphorylation of the signal transducer and activator of transcription 5 proteins. We confirmed previous studies that 2 hours suckling resulted in a widespread induction of pSTAT5 in some forebrain regions such as the arcuate nucleus, the para- and periventricular nuclei, the medial preoptic area, the bed nucleus of the stria terminalis, and the medial amygdala.
doi:10.1016/j.npep.2017.02.057