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

The DOI matches its Crossref record; 42 of the 45 references it cites were found in a registry or an index, and 3 are not checked yet.

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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Crossref · 10.1038/nn1656

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  1. 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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Metadata

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
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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