Cited by 828Regulation of Appetite and ObesityNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

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Ghrelin controls hippocampal spine synapse density and memory performance

Diano, Sabrina, Farr, Susan A, Benoit, Stephen C, McNay, Ewan C, da Silva, Ivaldo, Horvath, Balazs, Gaskin, F Spencer, Nonaka, Naoko, Jaeger, Laura B, Banks, William A, Morley, John E, Pinto, Shirly, Sherwin, Robert S, Xu, Lin, Yamada, Kelvin A, Sleeman, Mark W, Tschöp, Matthias H, Horvath, Tamas L·2006·Nature Neuroscience

DOI 10.1038/nn1656

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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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Background
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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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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: Diano, Sabrina
Farr, Susan A
McNay, Ewan C
Nonaka, Naoko
Banks, William A
Morley, John E
Pinto, Shirly
Xu, Lin
Sleeman, Mark W
Tschöp, Matthias H
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2006-02-19
Volume: 9
Issue: 3
Pages: 381-388
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn1656
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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Ghrelin controls hippocampal spine synapse density and memory performance

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