Ghrelin controls hippocampal spine synapse density and memory performance
Abstract
The gut hormone and neuropeptide ghrelin affects energy balance and growth hormone release through hypothalamic action that involves synaptic plasticity in the melanocortin system. Ghrelin binding is also present in other brain areas, including the telencephalon, where its function remains elusive. Here we report that circulating ghrelin enters the hippocampus and binds to neurons of the hippocampal formation, where it promotes dendritic spine synapse formation and generation of long-term potentiation. These ghrelin-induced synaptic changes are paralleled by enhanced spatial learning and memory. Targeted disruption of the gene that encodes ghrelin resulted in decreased numbers of spine synapses in the CA1 region and impaired performance of mice in behavioral memory testing, both of which were rapidly reversed by ghrelin administration. Our observations reveal an endogenous function of ghrelin that links metabolic control with higher brain functions and suggest novel therapeutic strategies to enhance learning and memory processes.
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Ghrelin can pass through the blood-brain barrier, directly affecting brain cells.
“It has been shown that ghrelin can pass through the blood–brain barrier, directly affecting brain cells [46, 48–50].”
From Protective PLCG2 variants associate with a delayed onset of Alzheimer’s disease among heterozygous APOE ε4 carriers (2026) · cites this paper as [50]
Cites
Ghrelin is a growth-hormone-releasing acylated peptide from stomach
Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H., & Kangawa, K. (1999) · Nature · doi:10.1038/45230 · Cited by 8,479 · see citing works
REGIONAL STUDIES OF CATECHOLAMINES IN THE RAT BRAIN‐I
Glowinski, J., & Iversen, L. L. (1966) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1966.tb09873.x · Cited by 5,436 · see citing works
Ghrelin induces adiposity in rodents
Tschöp, M., Smiley, D. L., & Heiman, M. L. (2000) · Nature · doi:10.1038/35038090 · Cited by 3,949 · see citing works
Self-citationA preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans
Cummings, D. E., Purnell, J. Q., Frayo, R. S., Schmidova, K., Wisse, B. E., & Weigle, D. S. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1714 · Cited by 2,940 · see citing works
Ghrelin: Structure and Function
Kojima, M., & Kangawa, K. (2005) · Physiological Reviews · doi:10.1152/physrev.00012.2004 · Cited by 2,810 · see citing works
The human hippocampus and spatial and episodic memory
Burgess, N., Maguire, E. A., & O'Keefe, J. (2002) · Neuron · doi:10.1016/s0896-6273(02)00830-9 · Cited by 2,401 · see citing works
Circulating Ghrelin Levels Are Decreased in Human Obesity
Tschöp, M. H., Weyer, C., Tataranni, P. A., Devanarayan, V., Ravussin, É., & Heiman, M. L. (2001) · Diabetes · doi:10.2337/diabetes.50.4.707 · Cited by 1,992 · see citing works
Self-citationCowley, M. A., Smith, R. G., Diano, S., Tschöp, M., Pronchuk, N., Grove, K. L., Strasburger, C. J., Bidlingmaier, M., Esterman, M., Heiman, M. L., et al. (2003) · Neuron · doi:10.1016/s0896-6273(03)00063-1 · Cited by 1,679 · see citing works
Self-citationBiological, Physiological, Pathophysiological, and Pharmacological Aspects of Ghrelin
van der Lely, A. J., Tschöp, M., Heiman, M. L., & Ghigo, E. (2004) · Endocrine Reviews · doi:10.1210/er.2002-0029 · Cited by 1,187 · see citing works
Self-citationGuan, X.-M., Yu, H., Palyha, O., McKee, K., Feighner, S., Sirinathsinghji, D., Smith, R. G., van der Ploeg, L., & Howard, A. (1997) · Brain Research. Molecular Brain Research · doi:10.1016/s0169-328x(97)00071-5 · Cited by 1,185 · see citing works
Rapid Rewiring of Arcuate Nucleus Feeding Circuits by Leptin
Pinto, S., Roseberry, A. G., Liu, H., Diano, S., Shanabrough, M., Cai, X., Friedman, J. M., & Horvath, T. L. (2004) · Science · doi:10.1126/science.1089459 · Cited by 987 · see citing works
Self-citationAn 18-Year Follow-up of Overweight and Risk of Alzheimer Disease
Gustafson, D., Rothenberg, E., Blennow, K., Steen, B., & Skoog, I. (2003) · Archives of Internal Medicine · doi:10.1001/archinte.163.13.1524 · Cited by 811 · see citing works
Banks, W. A., Tschöp, M., Robinson, S. M., & Heiman, M. L. (2002) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.034827 · Cited by 691 · see citing works
Self-citationMice lacking ghrelin receptors resist the development of diet-induced obesity
Zigman, J. M. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26002 · Cited by 654 · see citing works
High-throughput engineering of the mouse genome coupled with high-resolution expression analysis
Valenzuela, D. M., Murphy, A. J., Frendewey, D. A., Gale, N. W., Economides, A. N., Auerbach, W., Poueymirou, W. T., Adams, N. C., Rojas, J., Yasenchak, J., et al. (2003) · Nature Biotechnology · doi:10.1038/nbt822 · Cited by 585 · see citing works
Minireview: Ghrelin and the Regulation of Energy Balance--A Hypothalamic Perspective
Horváth, T. L., Diano, S., Sótonyi, P., Heiman, M. L., & Tschöp, M. H. (2001) · Endocrinology · doi:10.1210/endo.142.10.8490 · Cited by 570 · see citing works
Self-citationSarter, M. F., Bodewitz, G., & Stephens, D. (1988) · Psychopharmacology · doi:10.1007/bf00212843 · Cited by 533 · see citing works
Ultrastructural evidence that hippocampal alpha estrogen receptors are located at extranuclear sites
Milner, T. A., McEwen, B. S., Hayashi, S., Li, C. J., Reagan, L. P., & Alves, S. E. (2000) · The Journal of Comparative Neurology · doi:10.1002/1096-9861(20010115)429:3 · Cited by 491 · see citing works
Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference
Wortley, K. E., Anderson, K. D., García, K., Murray, J. D., Malinova, L., Liu, R., Moncrieffe, M., Thabet, K., Cox, H. J., Yancopoulos, G. D., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402763101 · Cited by 471 · see citing works
Self-citationMcNay, E. C., Fries, T. M., & Gold, P. E. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.050583697 · Cited by 386 · see citing works
Self-citationAbsence of ghrelin protects against early-onset obesity
Wortley, K. E. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26003 · Cited by 375 · see citing works
Li, C., Brake, W. G., Romeo, R. D., Dunlop, J. C., Gordon, M., Buzescu, R., Magariños, A. M., Allen, P. B., Greengard, P., Luine, V. N., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307313101 · Cited by 345 · see citing works
Plasma ghrelin concentrations in elderly subjects: comparison with anorexic and obese patients.
Rigamonti, A., Pincelli, A. I., Corrà, B., Viarengo, R., Bonomo, S., Galimberti, D., Scacchi, M., Scarpini, E., Cavagnini, F., & Müller, E. (2002) · Journal of Endocrinology · doi:10.1677/joe.0.175r001 · Cited by 306 · see citing works
Impaired recognition memory in patients with lesions limited to the hippocampal formation.
Reed, J. M., & Squire, L. R. (1997) · Behavioral Neuroscience · doi:10.1037//0735-7044.111.4.667 · Cited by 295 · see citing works
Impaired recognition memory in patients with lesions limited to the hippocampal formation.
Reed, J. M., & Squire, L. R. (1997) · Behavioral Neuroscience · doi:10.1037/0735-7044.111.4.667 · Cited by 229 · see citing works
Wu, A., Molteni, R., Ying, Z., & Gómez‐Pinilla, F. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00154-4 · Cited by 223 · see citing works
β-Amyloid precursor polypeptide in SAMP8 mice affects learning and memory
Morley, J. E., Kumar, V. B., Bernardo, A. E., Farr, S. A., Uezu, K., Tumosa, N., & Flood, J. F. (2000) · Peptides · doi:10.1016/s0196-9781(00)00342-9 · Cited by 222 · see citing works
Self-citationMcNay, E. C., McCarty, R. C., & Gold, P. E. (2001) · Neurobiology of Learning and Memory · doi:10.1006/nlme.2000.3976 · Cited by 200 · see citing works
Self-citationKetone bodies do not directly alter excitatory or inhibitory hippocampal synaptic transmission
Thio, L. L., Wong, M. L., & Yamada, K. A. (2000) · Neurology · doi:10.1212/wnl.54.2.325 · Cited by 146 · see citing works
Self-citationMcNay, E. C., & Gold, P. E. (2001) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/56.2.b66 · Cited by 132 · see citing works
Self-citationRagozzino, M. E., & Gold, P. E. (1995) · Neuroscience · doi:10.1016/0306-4522(95)00204-v · Cited by 111 · see citing works
Myhrer, T. (1988) · Behavioral Neuroscience · doi:10.1037//0735-7044.102.3.356 · Cited by 79 · see citing works
Ragozzino, M. E., Parker, M., & Gold, P. E. (1992) · Brain Research · doi:10.1016/0006-8993(92)91480-3 · Cited by 72 · see citing works
Myhrer, T. (1988) · Behavioral Neuroscience · doi:10.1037/0735-7044.102.3.356 · Cited by 69 · see citing works
Ghrelin as a Potential Anti-Obesity Target
Horváth, T. L., Castañeda, T. R., Tang‐Christensen, M., Pagotto, U., & Tschöp, M. H. (2003) · Current Pharmaceutical Design · doi:10.2174/1381612033454748 · Cited by 68 · see citing works
Self-citationEffects of opioid microinjections into the medial septal area on spatial memory in rats.
Bostock, E., Gallagher, M., & King, R. A. (1988) · Behavioral Neuroscience · doi:10.1037//0735-7044.102.5.643 · Cited by 68 · see citing works
McNay, E. C., & Gold, P. E. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-10-03853.1998 · Cited by 62 · see citing works
Self-citationRagozzino, M. E., Wenk, G. L., & Gold, P. E. (1994) · Brain Research · doi:10.1016/0006-8993(94)91599-7 · Cited by 61 · see citing works
Is ghrelin a signal for the development of metabolic systems?
Grove, K. L. (2005) · Journal of Clinical Investigation · doi:10.1172/jci27211 · Cited by 57 · see citing works
Farr, S. A., Banks, W. A., Scola, M. E. L., Flood, J. F., & Morley, J. E. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02495-1 · Cited by 48 · see citing works
Self-citationRagozzino, M. E., Hellems, K. L., Lennartz, R. C., et al. (1995) · Behavioral Neuroscience · doi:10.1037//0735-7044.109.6.1074 · Cited by 45 · see citing works
Ragozzino, M. E., Hellems, K. L., Lennartz, R. C., et al. (1995) · Behavioral Neuroscience · doi:10.1037/0735-7044.109.6.1074 · Cited by 39 · see citing works
Wan, R., Givens, B. S., & Olton, D. S. (1995) · Neurobiology of Learning and Memory · doi:10.1006/nlme.1995.1007 · Cited by 21 · see citing works
Attenuation of Morphine-Induced Behavioral Changes in Rodents byd-andl-Glucose
Talley, C. P., Arankowsky‐Sandoval, G., McCarty, R. C., et al. (1999) · Neurobiology of Learning and Memory · doi:10.1006/nlme.1998.3861 · Cited by 18 · see citing works
Seyler, D. E., Dodge, J. A., Osborne, J. J., et al. (2000) · Drug Development Research · doi:10.1002/1098-2299(200004)49:4 · Cited by 13 · see citing works
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- van der Lely, A.J., Tschop, M., Heiman, M.L. & Ghigo, E. Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr. Rev. 25, 426–457 (2004). · DOI · Paper page
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Critchley, H. D., & Harrison, N. A. (2013) · Neuron · doi:10.1016/j.neuron.2013.02.008 · Cited by 1,177 · see citing works
Müller, T. D., Nogueiras, R., Andermann, M. L., Andrews, Z. B., Anker, S. D., Argente, J., Batterham, R. L., Benoit, S. C., Bowers, C. Y., Broglio, F., et al. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.03.005 · Cited by 1,034 · see citing works
Self-citationAbizaid, A., Liu, Z.-W., Andrews, Z. B., Shanabrough, M., Borok, E., Elsworth, J. D., Roth, R. H., Sleeman, M. W., Picciotto, M. R., Tschöp, M. H., et al. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29867 · Cited by 984 · see citing works
Self-citationGut hormones and the regulation of energy homeostasis
Murphy, K. G., & Bloom, S. R. (2006) · Nature · doi:10.1038/nature05484 · Cited by 778 · see citing works
Stranahan, A., Norman, E., Lee, K., Cutler, R., Telljohann, R., Egan, J., & Mattson, M. P. (2008) · Hippocampus · doi:10.1002/hipo.20470 · Cited by 755 · see citing works
UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals
Andrews, Z. B., Liu, Z.-W., Walllingford, N., Erion, D. M., Borok, E., Friedman, J. M., Tschöp, M. H., Shanabrough, M., Cline, G., Shulman, G. I., et al. (2008) · Nature · doi:10.1038/nature07181 · Cited by 710 · see citing works
Self-citationGhrelin Modulates Brain Activity in Areas that Control Appetitive Behavior
Malik, S., McGlone, F., Bedrossian, D., & Dagher, A. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.03.007 · Cited by 677 · see citing works
The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress
Lutter, M., Sakata, I., Osborne-Lawrence, S., Rovinsky, S. A., Anderson, J. G., Jung, S., Birnbaum, S., Yanagisawa, M., Elmquist, J. K., Nestler, E. J., et al. (2008) · Nature Neuroscience · doi:10.1038/nn.2139 · Cited by 644 · see citing works
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The road to restoring neural circuits for the treatment of Alzheimer's disease
Canter, R. G., Penney, J., & Tsai, L.-H. (2016) · Nature · doi:10.1038/nature20412 · Cited by 565 · see citing works
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Estrogen: A master regulator of bioenergetic systems in the brain and body
Rettberg, J. R., Yao, J., & Brinton, R. D. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2013.08.001 · Cited by 534 · see citing works
Horváth, T. L., Sármán, B., García‐Cáceres, C., Enriori, P. J., Sótonyi, P., Shanabrough, M., Borók, E., Argente, J., Chowen, J. A., Pérez–Tilve, D., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004282107 · Cited by 446 · see citing works
Self-citationNeuronal Regulation of Energy Homeostasis: Beyond the Hypothalamus and Feeding
Waterson, M. J., & Horváth, T. L. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.026 · Cited by 439 · see citing works
Obesity and cognitive decline: role of inflammation and vascular changes
Nguyen, J. C. D., Killcross, S., & Jenkins, T. A. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00375 · Cited by 429 · see citing works
Sarcopenia: Diagnosis and treatment
Morley, J. E. (2008) · The journal of nutrition health & aging · doi:10.1007/bf02982705 · Cited by 398 · see citing works
Self-citationBrain Regulation of Appetite and Satiety
Ahima, R. S., & Antwi, D. A. (2008) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2008.08.005 · Cited by 387 · see citing works
Obesity and Hypertriglyceridemia Produce Cognitive Impairment
Farr, S. A., Yamada, K. A., Butterfield, D. A., Abdul, H. M., Xu, L., Miller, N. E., Banks, W. A., & Morley, J. E. (2008) · Endocrinology · doi:10.1210/en.2007-1722 · Cited by 382 · see citing works
Self-citationGómez‐Pinilla, F., Vaynman, S., & Ying, Z. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06524.x · Cited by 379 · see citing works
Ghrelin Increases the Rewarding Value of High-Fat Diet in an Orexin-Dependent Manner
Perelló, M., Sakata, I., Birnbaum, S. G., Chuang, J.-C., Osborne-Lawrence, S. L., Rovinsky, S. A., Wołoszyn, J., Yanagisawa, M., Lutter, M. L., & Zigman, J. M. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.10.030 · Cited by 369 · see citing works
Enhancement of Learning and Memory by Elevating Brain Magnesium
Slutsky, I., Abumaria, N., Wu, L., Huang, C., Zhang, L., Li, B., Zhao, X., Govindarajan, A., Zhao, M., Zhuo, M., et al. (2010) · Neuron · doi:10.1016/j.neuron.2009.12.026 · Cited by 372 · see citing works
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Leptin signaling in astrocytes regulates hypothalamic neuronal circuits and feeding
Kim, J. G., Suyama, S., Koch, M., Jin, S., Argente-Arizon, P., Argente, J., Liu, Z.-W., Zimmer, M. R., Jeong, J. K., Szigeti-Buck, K., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3725 · Cited by 336 · see citing works
Self-citationGhrelin directly targets the ventral tegmental area to increase food motivation.
Skibicka, K., Hansson, C., Álvarez-Crespo, M., Friberg, P., & Dickson, S. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.02.016 · Cited by 323 · see citing works
Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism
García‐Cáceres, C., Balland, É., Prévot, V., Luquet, S. H., Woods, S. C., Koch, M., Horváth, T. L., Yi, C., Chowen, J. A., Verkhratsky, A., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0286-y · Cited by 326 · see citing works
Self-citationRapid sensing of circulating ghrelin by hypothalamic appetite-modifying neurons
Schaeffer, M., Langlet, F., Lafont, C., Molino, F., Hodson, D. J., Roux, T., Lamarque, L., Verdié, P., Bourrier, E., Dehouck, B., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1212137110 · Cited by 325 · see citing works
The Homeostatic Force of Ghrelin
Yanagi, S., Sato, T., Kangawa, K., & Nakazato, M. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.008 · Cited by 324 · see citing works
Diet-Induced Obesity Causes Ghrelin Resistance in Arcuate NPY/AgRP Neurons
Briggs, D. I., Enriori, P. J., Lemus, M. B., Cowley, M. A., & Andrews, Z. B. (2010) · Endocrinology · doi:10.1210/en.2010-0556 · Cited by 320 · see citing works
Vagal and hormonal gut-brain communication: from satiation to satisfaction
Berthoud, H. ‐. (2008) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2008.01104.x · Cited by 307 · see citing works
Metabolic Dysfunction in Alzheimers Disease and Related Neurodegenerative Disorders
Cai, H., Cong, W., Ji, S., Rothman, S. M., Maudsley, S. R., & Martin, B. (2012) · Current Alzheimer Research · doi:10.2174/156720512799015064 · Cited by 308 · see citing works
Liu, T., Kong, D., Shah, B. P., Ye, C., Koda, S., Saunders, A., Ding, J. B., Yang, Z., Sabatini, B. L., & Lowell, B. B. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.027 · Cited by 296 · see citing works
Andrews, Z. B., Erion, D., Beiler, R., Liu, Z.-W., Abizaid, A., Zigman, J., Elsworth, J. D., Savitt, J. M., DiMarchi, R., Tschöp, M., et al. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3890-09.2009 · Cited by 289 · see citing works
Self-citationChanging perspectives regarding late-life dementia
Fotuhi, M., Hachinski, V., & Whitehouse, P. J. (2009) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.175 · Cited by 291 · see citing works
Zheng, H., Lenard, N. R., Shin, A. C., & Berthoud, H. R. (2009) · International Journal of Obesity · doi:10.1038/ijo.2009.65 · Cited by 286 · see citing works
Food reward, hyperphagia, and obesity
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Kanoski, S. E., & Grill, H. J. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.09.011 · Cited by 278 · see citing works
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Lv, Z., Zhou, Y., Han, S., & Roy, V. A. L. (2018) · Materials Today · doi:10.1016/j.mattod.2017.12.001 · Cited by 263 · see citing works
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Mora, F., Segovia, G., del Arco, A., de Blas, M., & Garrido, P. (2012) · Brain Research · doi:10.1016/j.brainres.2011.12.049 · Cited by 253 · see citing works
Microbial ecology and host-microbiota interactions during early life stages
Collado, M. C., Cernada, M., Bäuerl, C., Vento, M., & Pérez‐Martínez, G. (2012) · Gut Microbes · doi:10.4161/gmic.21215 · Cited by 254 · see citing works
Skibicka, K., Hansson, C., Egecioglu, E., & Dickson, S. (2012) · Addiction Biology · doi:10.1111/j.1369-1600.2010.00294.x · Cited by 258 · see citing works
Regulation of dietary choice by the decision-making circuitry
Rangel, A. (2013) · Nature Neuroscience · doi:10.1038/nn.3561 · Cited by 246 · see citing works
The impact of gut hormones on the neural circuit of appetite and satiety: A systematic review
Zanchi, D., Depoorter, A., Egloff, L., Haller, S., Mählmann, L., Lang, U. E., Drewe, J., Beglinger, C., Schmidt, A., & Borgwardt, S. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.06.013 · Cited by 243 · see citing works
Ghrelin Gene Products and the Regulation of Food Intake and Gut Motility
Chen, C., Asakawa, A., Fujimiya, M., Lee, S., & Inui, A. (2009) · Pharmacological Reviews · doi:10.1124/pr.109.001958 · Cited by 239 · see citing works
Hypothalamic control of energy balance: insights into the role of synaptic plasticity
Dietrich, M. O., & Horvath, T. L. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2012.12.005 · Cited by 227 · see citing works
Vaccination against weight gain
Zorrilla, E. P., Iwasaki, S., Moss, J. A., Chang, J. Y., Otsuji, J., Inoue, K., Meijler, M. M., & Janda, K. D. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605376103 · Cited by 224 · see citing works
Pathophysiology of anorexia in the cancer cachexia syndrome
Ezeoke, C., & Morley, J. E. (2015) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12059 · Cited by 224 · see citing works
Self-citationKanoski, S. E., Fortin, S. M., Ricks, K. M., & Grill, H. J. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.07.002 · Cited by 205 · see citing works
Ghrelin promotes thymopoiesis during aging
Dixit, V. D., Yang, H., Sun, Y., Weeraratna, A. T., Youm, Y., Smith, R. G., & Taub, D. D. (2007) · Journal of Clinical Investigation · doi:10.1172/jci30248 · Cited by 204 · see citing works
Contributions of the hippocampus and medial prefrontal cortex to energy and body weight regulation
Davidson, T. L., Chan, K., Jarrard, L. E., Kanoski, S. E., Clegg, D. J., & Benoit, S. C. (2008) · Hippocampus · doi:10.1002/hipo.20499 · Cited by 204 · see citing works
Self-citationLimitations in anti-obesity drug development: the critical role of hunger-promoting neurons
Dietrich, M. O., & Horváth, T. L. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3739 · Cited by 202 · see citing works
Ghrelin inhibits apoptosis in hypothalamic neuronal cells during oxygen-glucose deprivation.
Chung, H., Kim, E., Lee, D.-H., Seo, S., Ju, S., Lee, D., Kim, H., & Park, S. (2007) · Endocrinology · doi:10.1210/en.2006-0991 · Cited by 213 · see citing works
Martin, B., Pearson, M., Kebejian, L., Golden, E., Keselman, A., Bender, M., Carlson, O., Egan, J., Ladenheim, B., Cadet, J.-L., et al. (2007) · Endocrinology · doi:10.1210/en.2007-0161 · Cited by 199 · see citing works
The extra-hypothalamic actions of ghrelin on neuronal function.
Andrews, Z. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2010.10.001 · Cited by 199 · see citing works
Monteleone, P., & Maj, M. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.10.021 · Cited by 193 · see citing works
Ferrini, F., Salio, C., Lossi, L., & Merighi, A. (2009) · Current Neuropharmacology · doi:10.2174/157015909787602779 · Cited by 197 · see citing works
Diabetes, Sarcopenia, and Frailty
Morley, J. E. (2008) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2008.03.004 · Cited by 186 · see citing works
Self-citationThe clinical significance of gastrointestinal changes with aging
Bhutto, A., & Morley, J. E. (2008) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32830b5d37 · Cited by 186 · see citing works
Self-citationAleman, A., & Torres‐Alemán, I. (2009) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2009.07.008 · Cited by 184 · see citing works
Simultaneous deletion of ghrelin and its receptor increases motor activity and energy expenditure
Pfluger, P. T., Kirchner, H., Günnel, S., Schrott, B., Pérez–Tilve, D., Fu, S., Benoit, S. C., Horváth, T. L., Joost, H., Wortley, K. E., et al. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00321.2007 · Cited by 182 · see citing works
Self-citationFrom Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation
Howick, K., Griffin, B. T., Cryan, J. F., & Schellekens, H. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18020273 · Cited by 178 · see citing works
Ghrelin Signalling on Food Reward: A Salient Link Between the Gut and the Mesolimbic System
Perelló, M., & Dickson, S. L. (2014) · Journal of Neuroendocrinology · doi:10.1111/jne.12236 · Cited by 170 · see citing works
Mani, B. K., Walker, A. K., López-Soto, E. J., Raingo, J., Lee, C. E., Perelló, M., Andrews, Z., & Zigman, J. (2014) · The Journal of comparative neurology · doi:10.1002/cne.23627 · Cited by 155 · see citing works
Dietrich, M. O., Andrews, Z. B., & Horváth, T. L. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2744-08.2008 · Cited by 172 · see citing works
Drug delivery to the brain in Alzheimer's disease: Consideration of the blood–brain barrier
Banks, W. A. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.12.005 · Cited by 184 · see citing works
Self-citationBrain circuits regulating energy homeostasis
Abizaid, A. B., & Horváth, T. L. (2008) · Regulatory Peptides · doi:10.1016/j.regpep.2007.10.006 · Cited by 171 · see citing works
Wang, G.-J., Yang, J., Volkow, N. D., Telang, F., Ma, Y., Zhu, W., Wong, C. T., Tomasi, D., Thanos, P. K., & Fowler, J. S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601977103 · Cited by 168 · see citing works
A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear
Meyer, R. M., Burgos-Robles, A., Liu, E., Correia, S. S., & Goosens, K. A. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.135 · Cited by 169 · see citing works
Recruiting adaptive cellular stress responses for successful brain ageing
Stranahan, A. M., & Mattson, M. P. (2012) · Nature reviews. Neuroscience · doi:10.1038/nrn3151 · Cited by 169 · see citing works
Álvarez-Crespo, M., Skibicka, K. P., Farkas, I., Molnár, C. S., Egecioglu, E., Hrabovszky, E., Liposits, Z., & Dickson, S. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0046321 · Cited by 166 · see citing works
Banks, W., Burney, B. O., & Robinson, S. (2008) · Peptides · doi:10.1016/j.peptides.2008.07.001 · Cited by 155 · see citing works
Self-citationThe blood–brain barrier as an endocrine tissue
Banks, W. A. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0213-7 · Cited by 162 · see citing works
Self-citationWalker, A. K., Rivera, P. D., Wang, Q., Chuang, J.-C., Tran, S., Osborne-Lawrence, S., Estill, S. J., Starwalt, R., Huntington, P., Morlock, L., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.34 · Cited by 161 · see citing works
Ghrelin, the peripheral hunger hormone
Higgins, S. C., Gueorguiev, M., & Korbonits, M. (2007) · Annals of Medicine · doi:10.1080/07853890601149179 · Cited by 158 · see citing works
Fuel utilization by hypothalamic neurons: roles for ROS.
Horvath, T., Andrews, Z., & Diano, S. (2009) · Trends in endocrinology and metabolism · doi:10.1016/j.tem.2008.10.003 · Cited by 159 · see citing works
Self-citationBlood-brain barrier disruption: mechanistic links between Western diet consumption and dementia
Hsu, T. M., & Kanoski, S. E. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00088 · Cited by 157 · see citing works
Obesity Impairs the Action of the Neuroendocrine Ghrelin System
Zigman, J. M., Bouret, S. G., & Andrews, Z. B. (2015) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2015.09.010 · Cited by 153 · see citing works
Shin, A. C., Zheng, H., & Berthoud, H. (2009) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.02.010 · Cited by 148 · see citing works
Bozdagi, O., Rich, E. L., Tronel, S., Sadahiro, M., Patterson, K., Shapiro, M. L., Alberini, C. M., Huntley, G. W., & Salton, S. R. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3145-08.2008 · Cited by 145 · see citing works
BDNF and the central control of feeding: accidental bystander or essential player?
Rios, M. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2012.12.009 · Cited by 152 · see citing works
The influences of diet and exercise on mental health through hormesis
Gómez‐Pinilla, F. (2007) · Ageing Research Reviews · doi:10.1016/j.arr.2007.04.003 · Cited by 149 · see citing works
Monteleone, A. M., Castellini, G., Volpe, U., Ricca, V., Lelli, L., Monteleone, P., & Maj, M. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.02.020 · Cited by 152 · see citing works
Synaptic plasticity in neuronal circuits regulating energy balance
Zeltser, L. M., Seeley, R. J., & Tschöp, M. H. (2012) · Nature Neuroscience · doi:10.1038/nn.3219 · Cited by 147 · see citing works
Self-citationGhrelin, a gastrointestinal hormone, regulates energy balance and lipid metabolism
Lv, Y., Liang, T., Wang, G., & Li, Z. (2018) · Bioscience Reports · doi:10.1042/bsr20181061 · Cited by 141 · see citing works
Ghrelin and Dopamine: New Insights on the Peripheral Regulation of Appetite
Abizaid, A. B. (2009) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2009.01896.x · Cited by 135 · see citing works
Ghrelin's Roles in Stress, Mood, and Anxiety Regulation
Chuang, J.-C., & Zigman, J. M. (2010) · International Journal of Peptides · doi:10.1155/2010/460549 · Cited by 135 · see citing works
Moon, M., Choi, J. G., Nam, D. W., Hong, H., Choi, Y.-J., Oh, M., & Mook-Jung, I. (2011) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-101263 · Cited by 131 · see citing works
Jaeger, L. B., Dohgu, S., Hwang, M. C., Farr, S., Murphy, M. P., Fleegal-DeMotta, M. A., Lynch, J. L., Robinson, S., Niehoff, M., Johnson, S. N., et al. (2009) · Journal of Alzheimer's Disease · doi:10.3233/jad-2009-1074 · Cited by 135 · see citing works
Self-citationEngel, J. A., & Jerlhag, E. (2014) · CNS Drugs · doi:10.1007/s40263-014-0178-y · Cited by 132 · see citing works
GABAergic signaling by AgRP neurons prevents anorexia via a melanocortin-independent mechanism
Wu, Q., & Palmiter, R. D. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.10.110 · Cited by 133 · see citing works
- Authors
- Diano, S., Farr, S. A., Benoit, S. C., McNay, E. C., da Silva, I., Horvath, B., Gaskin, F. S., Nonaka, N., Jaeger, L. B., Banks, W. A., Morley, J. E., Pinto, S., Sherwin, R. S., Xu, L., Yamada, K. A., Sleeman, M. W., Tschöp, M. H., & Horvath, T. L.
- Affiliations
- Yale University (US)
- St. Louis VA Medical Center (US)
- University of Cincinnati (US)
- Howard Hughes Medical Institute (US)
- Washington University in St. Louis (US)
- Regeneron (United States) (US)
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2006-02-19
- Volume
- 9
- Issue
- 3
- Pages
- 381-388
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2154294326
- Semantic Scholar
- ed71645a1b530393f2d3862ed437ab76250f7ac4
- Cited by
- 828
- References
- 43
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 24 · 2023: 19 · 2022: 46 · 2021: 39 · 2020: 29 · 2019: 38 · 2018: 48 · 2017: 49 · 2016: 33 · 2015: 48 · 2014: 46 · 2013: 75 · 2012: 48
- FWCI
- 21.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (R01AA012743, AA12743)
- National Institute on Aging (AG-22880, R01AG022880)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK7386, DK61619, DK60711, R01DK070039, DK70039, R01DK060711, R01DK061619, T35DK007386)
- National Institute of Neurological Disorders and Stroke (R01NS041725, NS-41725, R01NS040525, NS 40525)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- ghrelin, hippocampus, dendritic spines, synaptogenesis, long-term potentiation, spatial learning and memory, CA1 region, growth hormone secretagogue receptor, energy balance
- MeSH terms
- Animals, Cell Differentiation, Hippocampus, Learning, Male, Memory, Memory Disorders, Mice, Inbred C57BL, Synaptic Transmission, Space Perception, Synapses, Rats, Sprague-Dawley, Long-Term Potentiation, Mice, Knockout, Nootropic Agents, Peptide Hormones, Dendritic Spines, Mice, Rats, Ghrelin
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