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L Francisco Lorenzo-Martín Centro de Investigación del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca, Salamanca, Spain

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Mauricio Menacho-Márquez Centro de Investigación del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca, Salamanca, Spain

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Salvatore Fabbiano Centro de Investigación del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Salamanca, Spain

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Omar Al-Massadi Departamento de Fisioloxía, University of Santiago de Compostela, Santiago de Compostela, Spain
Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, University of Santiago de Compostela, Santiago de Compostela, Spain
Centro de Investigación Biomédica en Red de Cáncer sobre la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), University of Santiago de Compostela, Santiago de Compostela, Spain

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Antonio Abad Centro de Investigación del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), CSIC-University of Salamanca, Salamanca, Spain

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Sonia Rodríguez-Fdez Centro de Investigación del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Salamanca, Spain

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María A Sevilla Centro de Investigación del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Salamanca, Spain

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María J Montero Centro de Investigación del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Salamanca, Spain

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Carlos Diéguez Departamento de Fisioloxía, University of Santiago de Compostela, Santiago de Compostela, Spain
Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, University of Santiago de Compostela, Santiago de Compostela, Spain
Centro de Investigación Biomédica en Red de Cáncer sobre la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), University of Santiago de Compostela, Santiago de Compostela, Spain

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Rubén Nogueiras Departamento de Fisioloxía, University of Santiago de Compostela, Santiago de Compostela, Spain
Centro de Investigación en Medicina Molecular e Enfermidades Crónicas, University of Santiago de Compostela, Santiago de Compostela, Spain
Centro de Investigación Biomédica en Red de Cáncer sobre la Fisiopatología de la Obesidad y Nutrición (CIBEROBN), University of Santiago de Compostela, Santiago de Compostela, Spain

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Xosé R Bustelo Centro de Investigación del Cáncer, CSIC-University of Salamanca, Salamanca, Spain
Instituto de Biología Molecular y Celular del Cáncer, CSIC-University of Salamanca, Salamanca, Spain

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-associated thermogenesis as well as to transient increases in blood pressure, ventilation activity and vasomotor tone ( Guyenet 2006 , Lambert et al. 2010 ). One of the key brainstem centers controlling the sympathetic outflow is the rostral ventrolateral medulla (RVLM

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Marc Schneeberger Diabetes and Obesity Research Laboratory, Department of Endocrinology and Nutrition, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
Diabetes and Obesity Research Laboratory, Department of Endocrinology and Nutrition, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
Diabetes and Obesity Research Laboratory, Department of Endocrinology and Nutrition, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain

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Ramon Gomis Diabetes and Obesity Research Laboratory, Department of Endocrinology and Nutrition, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
Diabetes and Obesity Research Laboratory, Department of Endocrinology and Nutrition, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
Diabetes and Obesity Research Laboratory, Department of Endocrinology and Nutrition, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain

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Marc Claret Diabetes and Obesity Research Laboratory, Department of Endocrinology and Nutrition, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
Diabetes and Obesity Research Laboratory, Department of Endocrinology and Nutrition, Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain

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involved in the homeostatic regulation of energy balance. The homeostatic system: hypothalamus and brainstem The hypothalamus: neuronal anatomy, nuclei, and neuropeptides Seminal lesioning studies conducted in rodents during the 1940s and 1950s highlighted

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Katie Wynne Endocrine Unit, Imperial College Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK

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Sarah Stanley Endocrine Unit, Imperial College Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK

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Barbara McGowan Endocrine Unit, Imperial College Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK

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Steve Bloom Endocrine Unit, Imperial College Faculty of Medicine, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK

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and body weight ( Rios et al. 2001 , Xu et al. 2003 ). Thus, VMH BDNF neurons may form another downstream pathway through which the melanocortin system regulates appetite and body weight. The brainstem pathways

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Katherine N Makowski Animal Care Program, University of California, San Diego, La Jolla, California, USA

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Michael J Kreisman Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Diego, La Jolla, California, USA

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Richard B McCosh Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Diego, La Jolla, California, USA

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Ali A Raad Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Diego, La Jolla, California, USA

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Kellie M Breen Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Diego, La Jolla, California, USA

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or IL-1β within the area postrema and norepinephrine-containing brainstem regions, as well as select hypothalamic nuclei associated with both HPA and reproductive axis function, including the paraventricular nucleus and dorsomedial nucleus ( Schiltz

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Eugen Brailoiu Department of Pharmacology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, Pennsylvania 19140, USA
Department of Pathology,
Division of Biocomputing, Department of Biochemistry and Molecular Biology and
Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA

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Siok L Dun Department of Pharmacology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, Pennsylvania 19140, USA
Department of Pathology,
Division of Biocomputing, Department of Biochemistry and Molecular Biology and
Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA

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G Cristina Brailoiu Department of Pharmacology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, Pennsylvania 19140, USA
Department of Pathology,
Division of Biocomputing, Department of Biochemistry and Molecular Biology and
Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA

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Keisuke Mizuo Department of Pharmacology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, Pennsylvania 19140, USA
Department of Pathology,
Division of Biocomputing, Department of Biochemistry and Molecular Biology and
Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA

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Larry A Sklar Department of Pharmacology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, Pennsylvania 19140, USA
Department of Pathology,
Division of Biocomputing, Department of Biochemistry and Molecular Biology and
Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA

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Tudor I Oprea Department of Pharmacology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, Pennsylvania 19140, USA
Department of Pathology,
Division of Biocomputing, Department of Biochemistry and Molecular Biology and
Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA

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Eric R Prossnitz Department of Pharmacology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, Pennsylvania 19140, USA
Department of Pathology,
Division of Biocomputing, Department of Biochemistry and Molecular Biology and
Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA

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Nae J Dun Department of Pharmacology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, Pennsylvania 19140, USA
Department of Pathology,
Division of Biocomputing, Department of Biochemistry and Molecular Biology and
Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA

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hypothalamus and brainstem. Even if GPR30 and ERβ are present in the paraventricular hypothalamic nucleus, they seem to be localized in different cell populations: ERβ is reported to be highly (60–80%) expressed in corticotropin releasing factor-positive cells

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Beverly A S Reyes Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
Department of Neurosurgery, Farber Institute for Neurosciences, Thomas Jefferson University, 900 Walnut Street, Suite 400, Philadelphia, Pennsylvania 19107, USA
Department of Biology, Washington and Lee University, Lexington, Virginia 24450-03, USA

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Hiroko Tsukamura Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
Department of Neurosurgery, Farber Institute for Neurosciences, Thomas Jefferson University, 900 Walnut Street, Suite 400, Philadelphia, Pennsylvania 19107, USA
Department of Biology, Washington and Lee University, Lexington, Virginia 24450-03, USA

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Helen I’Anson Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
Department of Neurosurgery, Farber Institute for Neurosciences, Thomas Jefferson University, 900 Walnut Street, Suite 400, Philadelphia, Pennsylvania 19107, USA
Department of Biology, Washington and Lee University, Lexington, Virginia 24450-03, USA

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Maria Amelita C Estacio Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
Department of Neurosurgery, Farber Institute for Neurosciences, Thomas Jefferson University, 900 Walnut Street, Suite 400, Philadelphia, Pennsylvania 19107, USA
Department of Biology, Washington and Lee University, Lexington, Virginia 24450-03, USA

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Kanjun Hirunagi Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
Department of Neurosurgery, Farber Institute for Neurosciences, Thomas Jefferson University, 900 Walnut Street, Suite 400, Philadelphia, Pennsylvania 19107, USA
Department of Biology, Washington and Lee University, Lexington, Virginia 24450-03, USA

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Kei-Ichiro Maeda Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
Department of Neurosurgery, Farber Institute for Neurosciences, Thomas Jefferson University, 900 Walnut Street, Suite 400, Philadelphia, Pennsylvania 19107, USA
Department of Biology, Washington and Lee University, Lexington, Virginia 24450-03, USA

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. Previous studies have demonstrated noradrenergic regulation of estrogen binding in the hypothalamus ( Blaustein et al. 1986 , Blaustein 1987 , Blaustein & Turcotte 1987 ). Noradrenergic neurons arising from the lower brainstem project to the PVN

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Rusana Simonoska
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Annika E Stenberg
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Maoli Duan Department of Otorhinolaryngology, Center for Hearing and Communication Research, Department of Biosciences and Nutrition, Department of Woman and Child Health, Department of Biology and Biochemistry, Karolinska Institutet and Karolinska University Hospital, 171 76 Stockholm, Sweden

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Konstantin Yakimchuk Department of Otorhinolaryngology, Center for Hearing and Communication Research, Department of Biosciences and Nutrition, Department of Woman and Child Health, Department of Biology and Biochemistry, Karolinska Institutet and Karolinska University Hospital, 171 76 Stockholm, Sweden

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Anders Fridberger Department of Otorhinolaryngology, Center for Hearing and Communication Research, Department of Biosciences and Nutrition, Department of Woman and Child Health, Department of Biology and Biochemistry, Karolinska Institutet and Karolinska University Hospital, 171 76 Stockholm, Sweden

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Lena Sahlin Department of Otorhinolaryngology, Center for Hearing and Communication Research, Department of Biosciences and Nutrition, Department of Woman and Child Health, Department of Biology and Biochemistry, Karolinska Institutet and Karolinska University Hospital, 171 76 Stockholm, Sweden

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Jan-Åke Gustafsson Department of Otorhinolaryngology, Center for Hearing and Communication Research, Department of Biosciences and Nutrition, Department of Woman and Child Health, Department of Biology and Biochemistry, Karolinska Institutet and Karolinska University Hospital, 171 76 Stockholm, Sweden
Department of Otorhinolaryngology, Center for Hearing and Communication Research, Department of Biosciences and Nutrition, Department of Woman and Child Health, Department of Biology and Biochemistry, Karolinska Institutet and Karolinska University Hospital, 171 76 Stockholm, Sweden

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Malou Hultcrantz
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therapy have slightly better hearing than non-substituted women ( Kilicdag et al . 2004 ), and it is well documented that in auditory brainstem response (ABR) audiometry, women have shorter latencies than men ( Jerger & Hall 1980 ). In addition, women

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Antonella Amato Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Palermo, Italy

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Sara Baldassano Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Palermo, Italy

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Flavia Mulè Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università di Palermo, Palermo, Italy

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also produced in a discrete population of neurons in the brainstem, which projects mainly to the hypothalamus, brain area that plays a key role in control of food intake ( Vrang et al. 2007 ). Prohormone convertase 1/3 (PC1/3) processes proglucagon in

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Riccardo Dore Department of Internal Medicine I, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany

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Luka Levata Department of Internal Medicine I, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany

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Hendrik Lehnert Department of Internal Medicine I, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany

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Carla Schulz Department of Internal Medicine I, Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, Lübeck, Germany

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example, in the hypothalamus and brainstem ( Oh-I et al. 2006 , Brailoiu et al. 2007 ) (for more details we refer to the respective sections). The product of the Nucb2 gene is a 420 AA peptide consisting of a 24 AA signal peptide and 396 AA

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Hiroki Otsubo Department of Physiology, Laboratory of Physiology, Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
Department of Physiology, Laboratory of Physiology, Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan

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Susumu Hyodo Department of Physiology, Laboratory of Physiology, Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan

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Hirofumi Hashimoto Department of Physiology, Laboratory of Physiology, Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan

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Makoto Kawasaki Department of Physiology, Laboratory of Physiology, Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan

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Hitoshi Suzuki Department of Physiology, Laboratory of Physiology, Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan

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Takeshi Saito Department of Physiology, Laboratory of Physiology, Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan

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Toyoaki Ohbuchi Department of Physiology, Laboratory of Physiology, Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan

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Toru Yokoyama Department of Physiology, Laboratory of Physiology, Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan

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Hiroaki Fujihara Department of Physiology, Laboratory of Physiology, Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan

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Tetsuro Matsumoto Department of Physiology, Laboratory of Physiology, Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan

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Yoshio Takei Department of Physiology, Laboratory of Physiology, Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan

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Yoichi Ueta Department of Physiology, Laboratory of Physiology, Department of Urology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan

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/l saline) followed by 4% paraformaldehyde and 0.2% picric acid in 0.1 M PB. Then the brains were removed, coronally cut, and divided into three blocks (forebrain, hypothalamus, and brainstem). The blocks were postfixed with 4% paraformaldehyde and 0

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