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The Journal of Neuroscience, January 1, 1998, 18(1):559-572
Leptin Receptor Immunoreactivity in Chemically Defined Target
Neurons of the Hypothalamus
Marie-Louise
Håkansson1,
Hilary
Brown1,
Nico
Ghilardi2,
Radek C.
Skoda2, and
Björn
Meister1
1 Department of Neuroscience, Karolinska Institute,
S-171 77 Stockholm, Sweden, and 2 Department of
Pharmacology, Biozentrum, University of Basel, 4056 Basel, Switzerland
The adipose tissue-derived hormone leptin regulates body weight
homeostasis by decreasing food intake and increasing energy expenditure. The weight-reducing action of leptin is thought to be
mediated primarily by signal transduction through the leptin receptor
(LR) in the hypothalamus. We have used immunohistochemistry to localize
LR-immunoreactive (LR-IR) cells in the rat brain using an antiserum
against a portion of the intracellular domain of LR that is common to
all LR isoforms. The antiserum recognized the short and long isoforms
of LR in transfected hematopoietic BaF3 cells. To examine the chemical
nature of target cells for leptin, direct double-labeling
immunofluorescence histochemistry was applied. The results show
extensive distribution of LR-like immunoreactivity (LR-LI) in the brain
with positively stained cells present, e.g., in the choroid plexus,
cerebral cortex, hippocampus, thalamus, and hypothalamus. In the
hypothalamus, strongly LR-IR neurons were present in the supraoptic
nucleus (SON) and paraventricular nucleus (PVN), periventricular
nucleus, arcuate nucleus, and lateral hypothalamus. Weaker LR-IR
neurons were also demonstrated in the lateral and medial preoptic
nuclei, suprachiasmatic nucleus, ventromedial and dorsomedial nuclei,
and tuberomammillary nucleus. Confocal laser scanning microscopy showed
LR-LI in the periphery of individual cells. In magnocellular neurons of
the SON and PVN, LR-LI was demonstrated in vasopressin- and
oxytocin-containing neurons. In parvocellular neurons of the PVN, LR-LI
was demonstrated in many corticotropin-releasing hormone-containing
neurons. LR-IR neurons were mainly seen in the ventromedial aspect of
the arcuate nucleus, where LR-LI co-localized with neuropeptide Y. In
the ventrolateral part of the arcuate nucleus, LR-LI was present in many large adrenocorticotropic hormone-IR
proopiomelanocortin-containing neurons and in a few galanin-,
neurotensin-, and growth hormone-releasing hormone-containing neurons.
In the dorsomedial arcuate nucleus, few tyrosine hydroxylase
(dopamine)-containing neurons were seen to have LR-LI.
Melanin-concentrating hormone-containing neurons in the lateral
hypothalamus had LR-LI. Based on the immunohistochemical results,
possible interactions of leptin with brain mechanisms are
discussed.
Key words:
arcuate nucleus; CRH; dopamine; galanin; GHRH; immunohistochemistry; lateral hypothalamic area; LHRH; MCH; neurotensin; NPY; oxytocin; paraventricular nucleus; POMC; somatostatin; supraoptic nucleus; vasopressin
Copyright © 1998 Society for Neuroscience 0270-6474/98/181559-14$05.00/0
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[Abstract]
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M. Shimizu-Albergine, D. L. Ippolito, and J. A. Beavo
Downregulation of Fasting-Induced cAMP Response Element-Mediated Gene Induction by Leptin in Neuropeptide Y Neurons of the Arcuate Nucleus
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February 15, 2001;
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[Abstract]
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P. Magni, L. Martini, and M. Motta
Leptin Actions on the Reproductive Axis
J. Clin. Endocrinol. Metab.,
February 1, 2001;
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P. D. Finn, M. J. Cunningham, D. G. Rickard, D. K. Clifton, and R. A. Steiner
Serotonergic Neurons Are Targets for Leptin in the Monkey
J. Clin. Endocrinol. Metab.,
January 1, 2001;
86(1):
422 - 426.
[Abstract]
[Full Text]
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R. Tamura, T. Kondoh, T. Ono, H. Nishijo, and K. Torii
Effects of Repeated Cold Stress on Activity of Hypothalamic Neurons in Rats During Performance of Operant Licking Task
J Neurophysiol,
December 1, 2000;
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2844 - 2858.
[Abstract]
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C. L. Adam, K. M. Moar, T. J. Logie, A. W. Ross, P. Barrett, P. J. Morgan, and J. G. Mercer
Photoperiod Regulates Growth, Puberty and Hypothalamic Neuropeptide and Receptor Gene Expression in Female Siberian Hamsters
Endocrinology,
December 1, 2000;
141(12):
4349 - 4356.
[Abstract]
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M.-L. Hakansson-Ovesjo, M. Collin, and B. Meister
Down-Regulated STAT3 Messenger Ribonucleic Acid and STAT3 Protein in the Hypothalamic Arcuate Nucleus of the Obese Leptin-Deficient (ob/ob) Mouse
Endocrinology,
November 1, 2000;
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[Abstract]
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K. Kawai, K. Sugimoto, K. Nakashima, H. Miura, and Y. Ninomiya
Leptin as a modulator of sweet taste sensitivities in mice
PNAS,
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(2000)
190066697.
[Abstract]
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E. Mihály, C. Fekete, J. B. Tatro, Z. Liposits, E. G. Stopa, and R. M. Lechan
Hypophysiotropic Thyrotropin-Releasing Hormone-Synthesizing Neurons in the Human Hypothalamus Are Innervated by Neuropeptide Y, Agouti-Related Protein, and {alpha}-Melanocyte-Stimulating Hormone
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July 1, 2000;
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M. C. Lebrethon, E. Vandersmissen, A. Gerard, A. S. Parent, J. L. Junien, and J. P. Bourguignon
In Vitro Stimulation of the Prepubertal Rat Gonadotropin-Releasing Hormone Pulse Generator by Leptin and Neuropeptide Y through Distinct Mechanisms
Endocrinology,
April 1, 2000;
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[Abstract]
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J. Iqbal, S. Pompolo, R. V. Considine, and I. J. Clarke
Localization of Leptin Receptor-Like Immunoreactivity in the Corticotropes, Somatotropes, and Gonadotropes in the Ovine Anterior Pituitary
Endocrinology,
April 1, 2000;
141(4):
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[Abstract]
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J. G. Hohmann, T. H. Teal, D. K. Clifton, J. Davis, V. J. Hruby, G. Han, and R. A. Steiner
Differential role of melanocortins in mediating leptin's central effects on feeding and reproduction
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J. G. Mercer, K. M. Moar, A. W. Ross, N. Hoggard, and P. J. Morgan
Photoperiod regulates arcuate nucleus POMC, AGRP, and leptin receptor mRNA in Siberian hamster hypothalamus
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M.-t. Liu, S. Seino, and A. L. Kirchgessner
Identification and Characterization of Glucoresponsive Neurons in the Enteric Nervous System
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J. Matsuda, I. Yokota, Y. Tsuruo, T. Murakami, K. Ishimura, K. Shima, and Y. Kuroda
Developmental Changes in Long-Form Leptin Receptor Expression and Localization in Rat Brain
Endocrinology,
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[Abstract]
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M. M. Hagan, P. J. Havel, R. J. Seeley, S. C. Woods, N. N. Ekhator, D. G. Baker, K. K. Hill, M. D. Wortman, A. H. Miller, R. L. Gingerich, et al.
Cerebrospinal Fluid and Plasma Leptin Measurements: Covariability with Dopamine and Cortisol in Fasting Humans
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A. Bernard, R. Cohen, S.-T. Khuth, B. Vedrine, O. Verlaeten, H. Akaoka, P. Giraudon, and M.-F. Belin
Alteration of the Leptin Network in Late Morbid Obesity Induced in Mice by Brain Infection with Canine Distemper Virus
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A. Inui
Cancer Anorexia-Cachexia Syndrome: Are Neuropeptides the Key?
Cancer Res.,
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[Abstract]
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A. Cai and J. F. Hyde
The Human Growth Hormone-Releasing Hormone Transgenic Mouse as a Model of Modest Obesity: Differential Changes in Leptin Receptor (OBR) Gene Expression in the Anterior Pituitary and Hypothalamus after Fasting and OBR Localization in Somatotrophs
Endocrinology,
August 1, 1999;
140(8):
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[Abstract]
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A. G. Watts, G. Sanchez-Watts, and A. B. Kelly
Distinct Patterns of Neuropeptide Gene Expression in the Lateral Hypothalamic Area and Arcuate Nucleus Are Associated with Dehydration-Induced Anorexia
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S. Reichlin
Editorial: Is Leptin a Secretion of the Brain?
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R. S. Ahima, C. Bjorbaek, S. Osei, and J. S. Flier
Regulation of Neuronal and Glial Proteins by Leptin: Implications for Brain Development
Endocrinology,
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B. Xu, P. S. Kalra, W. G. Farmerie, and S. P. Kalra
Daily Changes in Hypothalamic Gene Expression of Neuropeptide Y, Galanin, Proopiomelanocortin, and Adipocyte Leptin Gene Expression and Secretion: Effects of Food Restriction
Endocrinology,
June 1, 1999;
140(6):
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[Abstract]
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B. E. Levin, A. A. Dunn-Meynell, and V. H. Routh
Brain glucose sensing and body energy homeostasis: role in obesity and diabetes
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[Abstract]
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E.-M. Kim, M. K. Grace, C. C. Welch, C. J. Billington, and A. S. Levine
STZ-induced diabetes decreases and insulin normalizes POMC mRNA in arcuate nucleus and pituitary in rats
Am J Physiol Regulatory Integrative Comp Physiol,
May 1, 1999;
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[Abstract]
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P. Magni, R. Vettor, C. Pagano, A. Calcagno, E. Beretta, E. Messi, M. Zanisi, L. Martini, and M. Motta
Expression of a Leptin Receptor in Immortalized Gonadotropin-Releasing Hormone-Secreting Neurons
Endocrinology,
April 1, 1999;
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[Abstract]
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S. P. Kalra, M. G. Dube, S. Pu, B. Xu, T. L. Horvath, and P. S. Kalra
Interacting Appetite-Regulating Pathways in the Hypothalamic Regulation of Body Weight
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T. L. Horvath, S. Diano, and A. N. van den Pol
Synaptic Interaction between Hypocretin (Orexin) and Neuropeptide Y Cells in the Rodent and Primate Hypothalamus: A Novel Circuit Implicated in Metabolic and Endocrine Regulations
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February 1, 1999;
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M. J. Cunningham, D. K. Clifton, and R. A. Steiner
Leptin's Actions on the Reproductive Axis: Perspectives and Mechanisms
Biol Reprod,
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[Abstract]
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Y.-k. Yang, D. A. Thompson, C. J. Dickinson, J. Wilken, G. S. Barsh, S. B. H. Kent, and I. Gantz
Characterization of Agouti-Related Protein Binding to Melanocortin Receptors
Mol. Endocrinol.,
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C. Broberger, J. Johansen, C. Johansson, M. Schalling, and T. Hokfelt
The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice
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C. Peyron, D. K. Tighe, A. N. van den Pol, L. de Lecea, H. C. Heller, J. G. Sutcliffe, and T. S. Kilduff
Neurons Containing Hypocretin (Orexin) Project to Multiple Neuronal Systems
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P. M. Smith, V. Mollaret, and A. V. Ferguson
Leptin acts in the rat hypothalamic paraventricular nucleus to induce gastric mucosal damage
Am J Physiol Regulatory Integrative Comp Physiol,
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P. D. Finn, M. J. Cunningham, K.-Y. F. Pau, H. G. Spies, D. K. Clifton, and R. A. Steiner
The Stimulatory Effect of Leptin on the Neuroendocrine Reproductive Axis of the Monkey
Endocrinology,
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A. N. van den Pol, X.-B. Gao, K. Obrietan, T. S. Kilduff, and A. B. Belousov
Presynaptic and Postsynaptic Actions and Modulation of Neuroendocrine Neurons by a New Hypothalamic Peptide, Hypocretin/Orexin
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G. S. Tannenbaum, W. Gurd, and M. Lapointe
Leptin Is a Potent Stimulator of Spontaneous Pulsatile Growth Hormone (GH) Secretion and the GH Response to GH-Releasing Hormone
Endocrinology,
September 1, 1998;
139(9):
3871 - 3875.
[Abstract]
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C. M. Kotz, J. E. Briggs, J. D. Pomonis, M. K. Grace, A. S. Levine, and C. J. Billington
Neural site of leptin influence on neuropeptide Y signaling pathways altering feeding and uncoupling protein
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August 1, 1998;
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[Abstract]
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K. Kawai, K. Sugimoto, K. Nakashima, H. Miura, and Y. Ninomiya
Leptin as a modulator of sweet taste sensitivities in mice
PNAS,
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97(20):
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[Abstract]
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L. J. Shanley, A. J. Irving, and J. Harvey
Leptin Enhances NMDA Receptor Function and Modulates Hippocampal Synaptic Plasticity
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December 15, 2001;
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